Scientists have developed a molecular “clock” that could reshape how pediatricians measure and monitor childhood growth and potentially allow for an earlier diagnosis of life-altering development disorders. The research, published this week in PNAS, describes how the addition of chemical tags to DNA over time can potentially be used to screen for developmental differences and health problems in children.
As the sole carrier of genetic information, DNA does not exist as a naked template in the eukaryotic genome; instead DNA exists as a chromatin structure amenable to the changing environment, especially during the sensitive period of childhood. Not surprisingly, many complex regulatory mechanisms act on chromatin to ensure that each cell expresses only the appropriate genes, duplicates its genome with high fidelity, divides only when required, and combats constant assaults on its DNA.
Failure in any of the mechanisms regulating these events can lead to a wide range of outcomes from altered developmental trajectories to complex diseases. Furthermore, a number of chromatin modifying proteins are involved in genetic susceptibility to diseases. The objective of our research is to understand the molecular mechanisms of epigenetic regulation in response to the environment. This is largely achieved through evaluating DNA methylation, histone variants, post-translational modification of histone, and nucleosome positioning. Additionally, genetic variation may interact with specific environments, imparting sensitivity or resilience, to ultimately alter epigenetics patterns and phenotypic outcomes.
Systematic evaluation and validation of reference and library selection methods for deconvolution of cord blood DNA methylation data
Kristina Gervin and Lucas A. Salas and Kelly M. Bakulski and Menno C. van Zelm and Devin C. Koestler and John K. Wiencke and Liesbeth Duijts and Henriëtte A. Moll and Karl T. Kelsey and Michael S. Kobor and Robert Lyle and Brock C. Christensen and Janine F. Felix and Meaghan J. Jones
Reversal of epigenetic aging and immunosenescent trends in humans
Gregory M. Fahy and Robert T. Brooke and James P. Watson and Zinaida Good and Shreyas S. Vasanawala and Holden Maecker and Michael D. Leipold and David T. S. Lin and Michael S. Kobor and Steve Horvath
Dynamic DNA methylation changes in the maternal oxytocin gene locus (OXT) during pregnancy predict postpartum maternal intrusiveness
Philipp Toepfer and Kieran J. O’Donnell and Sonja Entringer and Elika Garg and Christine M. Heim and David T.S. Lin and Julia L. MacIsaac and Michael S. Kobor and Michael J. Meaney and Nadine Provençal and Elisabeth B. Binder and Pathik D. Wadhwa and Claudia Buss
Glutaminase Deficiency Caused by Short Tandem Repeat Expansion in GLS.
The New England journal of medicine
van Kuilenburg ABP and Tarailo-Graovac M and Richmond PA and Drögemöller BI and Pouladi MA and Leen R and Brand-Arzamendi K and Dobritzsch D and Dolzhenko E and Eberle MA and van Karnebeek CDM
A biologically-informed polygenic score identifies endophenotypes and clinical conditions associated with the insulin receptor function on specific brain regions.
Hari Dass SA and McCracken K and Pokhvisneva I and Chen LM and Garg E and Nguyen TTT and Wang Z and Barth B and Yaqubi M and McEwen LM and MacIsaac JL and Diorio J and Kobor MS and Silveira PP
Systematic evaluation and validation of reference and library selection methods for deconvolution of cord blood DNA methylation data
Gervin K and Salas LA and Bakulski KM and van Zelm MC and Koestler DC and Wiencke JK and Duijts L and Moll HA and Kelsey KT and Kobor MS and Lyle R and Christensen BC and Felix J and Jones MJ
A Role of Oxytocin Receptor Gene Brain Tissue Expression Quantitative Trait Locus rs237895 in the Intergenerational Transmission of the Effects of Maternal Childhood Maltreatment.
Journal of the American Academy of Child and Adolescent Psychiatry
Toepfer P and O Donnell KJ and Entringer S and Heim CM and Lin DTS and MacIsaac JL and Kobor MS and Meaney MJ and Provençal N and Binder EB and Wadhwa PD and Buss C
Analysis of two birth tissues provides new insights into the epigenetic landscape of neonates born preterm.
Wu Y and Lin X and Lim IY and Chen L and Teh AL and MacIsaac JL and Tan KH and Kobor MS and Chong YS and Gluckman PD and Karnani N
Genome-wide analysis of DNA methylation in relation to socioeconomic status during development and early adulthood.
American journal of physical anthropology
McDade TW and Ryan CP and Jones MJ and Hoke MK and Borja J and Miller GE and Kuzawa CW and Kobor MS
Integration of DNA methylation patterns and genetic variation in human pediatric tissues help inform EWAS design and interpretation.
Epigenetics & chromatin
Islam SA and Goodman SJ and MacIsaac JL and Obradovic J and Barr RG and Boyce WT and Kobor MS
Maternal Metabolic Complications in Pregnancy and Offspring Behavior Problems at 2 Years of Age.
Maternal and child health journal
Krzeczkowski JE and Lau A and Fitzpatrick J and Tamana S and Smithson L and de Souza R and Kozyrskyj AL and Lefebvre D and Becker AB and Subbarao P and Turvey SE and Pei J and CHILD Study Investigators
Reproduction predicts shorter telomeres and epigenetic age acceleration among young adult women
Calen P. Ryan and M. Geoffrey Hayes and Nanette R. Lee and Thomas W. McDade and Meaghan J. Jones and Michael S. Kobor and Christopher W. Kuzawa and Dan T. A. Eisenberg
Residential green space and pathways to term birth weight in the Canadian Healthy Infant Longitudinal Development (CHILD) Study.
International journal of health geographics
Cusack L and Sbihi H and Larkin A and Chow A and Brook JR and Moraes T and Mandhane PJ and Becker AB and Azad MB and Subbarao P and Kozyrskyj A and Takaro TK and Sears MR and Turvey SE and CHILD Study Investigators
Prenatal Alcohol Exposure: Profiling Developmental DNA Methylation Patterns in Central and Peripheral Tissues.
Frontiers in genetics
Lussier AA and Bodnar TS and Mingay M and Morin AM and Hirst M and Kobor MS and Weinberg J
Exploring the genetic basis of human population differences in DNA methylation and their causal impact on immune gene regulation.
Husquin LT and Rotival M and Fagny M and Quach H and Zidane N and McEwen LM and MacIsaac JL and Kobor MS and Aschard H and Patin E and Quintana-Murci L
Maternal psychosocial risk factors and offspring gestational epigenetic age acceleration in a South African birth cohort study
Koen N and Jones M and Nhapi RT and Donald KA and Barnett W and Hoffman N and MacIsaac JL and Morin AM and Lin DT and Kobor MS and Koenen KC and Zar HJ and Stein DJ
Early-life socioeconomic disadvantage, not current, predicts accelerated epigenetic aging of monocytes
Makeda K. Austin and Edith Chen and Kharah M. Ross and Lisa M. McEwen and Julia L. Maclsaac and Michael S. Kobor and Gregory E. Miller
Early post-conception maternal cortisol, children's HPAA activity and DNA methylation profiles.
Journal of developmental origins of health and disease
Barha CK and Salvante KG and Jones MJ and Farré P and Blais J and Kobor MS and Zeng L and Emberly E and Nepomnaschy PA
Diagnosing atopic dermatitis in infancy: Questionnaire reports vs criteria-based assessment.
Paediatric and perinatal epidemiology
Dharma C and Lefebvre DL and Tran MM and Lu Z and Lou WYW and Subbarao P and Becker AB and Mandhane PJ and Turvey SE and Moraes TJ and Azad MB and Sears MR and CHILD Study Investigators
The biological embedding of early-life socioeconomic status and family adversity in children's genome-wide DNA methylation.
Bush NR and Edgar RD and Park M and MacIsaac JL and McEwen LM and Adler NE and Essex MJ and Kobor MS and Boyce WT
Exposure to childhood abuse is associated with human sperm DNA methylation.
Roberts AL and Gladish N and Gatev E and Jones MJ and Chen Y and MacIsaac JL and Tworoger SS and Austin SB and Tanrikut C and Chavarro JE and Baccarelli AA and Kobor MS
Cell type-specific DNA methylation in neonatal cord tissue and cord blood: a 850K-reference panel and comparison of cell types.
Lin X and Tan JYL and Teh AL and Lim IY and Liew SJ and MacIsaac JL and Chong YS and Gluckman PD and Kobor MS and Cheong CY and Karnani N
Systematic evaluation of DNA methylation age estimation with common preprocessing methods and the Infinium MethylationEPIC BeadChip array.
McEwen LM and Jones MJ and Lin DTS and Edgar RD and Husquin LT and MacIsaac JL and Ramadori KE and Morin AM and Rider CF and Carlsten C and Quintana-Murci L and Horvath S and Kobor MS
Variably methylated regions in the newborn epigenome: environmental, genetic and combined influences
Czamara D and Eraslan G and Lahti J and Page CM and Lahti-Pulkkinen M and Hämäläinen E and Kajantie E and Laivuori H and Villa PM and Reynolds RM and Nystad W and Haberg SE and Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
Children's biobehavioral reactivity to challenge predicts DNA methylation in adolescence and emerging adulthood.
Goodman SJ and Roubinov DS and Bush NR and Park M and Farré P and Emberly E and Hertzman C and Essex MJ and Kobor MS and Boyce WT
Variability in DNA methylation at the serotonin transporter gene promoter: epigenetic mechanism or cell-type artifact?
Sarah R. Moore and Michael S. Kobor
The early care environment and DNA methylome variation in childhood.
Development and psychopathology
Garg E and Chen L and Nguyen TTT and Pokhvisneva I and Chen LM and Unternaehrer E and MacIsaac JL and McEwen LM and Mah SM and Gaudreau H and Levitan R and Moss E and Sokolowski MB and Mavan Study Team
An epigenetic pathway approach to investigating associations between prenatal exposure to maternal mood disorder and newborn neurobehavior.
Development and psychopathology
Conradt E and Adkins DE and Crowell SE and Monk C and Kobor MS
PRS-on-Spark (PRSoS): a novel, efficient and flexible approach for generating polygenic risk scores.
Chen LM and Yao N and Garg E and Zhu Y and Nguyen TTT and Pokhvisneva I and Hari Dass SA and Unternaehrer E and Gaudreau H and Forest M and McEwen LM and MacIsaac JL and Kobor MS and O'Donnell KJ
Comparison of DNA methylation measured by Illumina 450K and EPIC BeadChips in blood of newborns and 14-year-old children.
Solomon O and MacIsaac J and Quach H and Tindula G and Kobor MS and Huen K and Meaney MJ and Eskenazi B and Barcellos LF and Holland N
Differences in DNA methylation of white blood cell types at birth and in adulthood reflect postnatal immune maturation and influence accuracy of cell type prediction
Jones M and Dinh L and Razzaghian HR and de Goede O and MacIsaac JL and Morin AM and Gervin K and Ng R and Duijts L and van Zelm MC and Moll HA and Lyle R and Robinson WP and Koestler DC and Kobor MS
Exploring the Genetic Basis of Human Population Differences in DNA Methylation and their Causal Impact on Immune Gene Regulation
Lucas T. Husquin and Maxime Rotival and Maud Fagny and Hélène Quach and Nora Zidane and Lisa M. McEwen and Julia L. MacIsaac and Michael S Kobor and Hugues Aschard and Etienne Patin and Lluis Quintana-Murci
Perinatally acquired HIV infection accelerates epigenetic aging in South African adolescents.
AIDS (London, England)
Horvath S and Stein DJ and Phillips N and Heany SJ and Kobor MS and Lin DTS and Myer L and Zar HJ and Levine AJ and Hoare J
Human milk oligosaccharide profiles and food sensitization among infants in the CHILD Study.
Miliku K and Robertson B and Sharma AK and Subbarao P and Becker AB and Mandhane PJ and Turvey SE and Lefebvre DL and Sears MR and CHILD Study Investigators and Bode L and Azad MB
Cysteinyl Leukotriene Receptor 1 and Health Effects of Particulate Exposure in Asthma.
Annals of the American Thoracic Society
Rabinovitch N and Jones MJ and Faino A and Strand M and Morin AM and MacIsaac J and Reynolds PR and Singh A and Kobor MS and Gelfand EW and Carlsten C
DNA methylation signatures in peripheral blood mononuclear cells from a lifestyle intervention for women at midlife: a pilot randomized controlled trial.
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme
McEwen LM and Gatev EG and Jones MJ and MacIsaac JL and McAllister MM and Goulding RE and Madden KM and Dawes MG and Kobor MS and Ashe MC
A novel, biologically-informed polygenic score reveals role of mesocorticolimbic insulin receptor gene network on impulsivity and addiction
McCracken K and Hari Dass SA and Pokhvisneva I and Chen LM and Garg E and Nguyen TT and Yaqubi M and McEwen LM and MacIsaac JL and Diorio J and Kobor MS and O'Donnell KJ and Meaney MJ and Silveira P
Predicting the atopic march: Results from the Canadian Healthy Infant Longitudinal Development Study.
The Journal of allergy and clinical immunology
Tran MM and Lefebvre DL and Dharma C and Dai D and Lou WYW and Subbarao P and Becker AB and Mandhane PJ and Turvey SE and Sears MR and Canadian Healthy Infant Longitudinal Development Study investigators
Patterns of allergic sensitization and atopic dermatitis from 1 to 3 years: Effects on allergic diseases.
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
Dharma C and Lefebvre DL and Tran MM and Lou WYW and Subbarao P and Becker AB and Mandhane PJ and Turvey SE and Sears MR and CHILD Study investigators
Healthy Foundations Study: a randomised controlled trial to evaluate biological embedding of early-life experiences.
Gonzalez A and Catherine N and Boyle M and Jack SM and Atkinson L and Kobor M and Sheehan D and Tonmyr L and Waddell C and MacMillan HL and Healthy Foundations Study Team
DNA methylome variation in a perinatal nurse-visitation program that reduces child maltreatment: a 27-year follow-up.
O'Donnell KJ and Chen L and MacIsaac JL and McEwen LM and Nguyen T and Beckmann K and Zhu Y and Chen LM and Brooks-Gunn J and Goldman D and Grigorenko EL and Leckman JF and Diorio J and Meaney MJ
Altered DNA methylation is associated with aberrant gene expression in parenchymal but not airway fibroblasts isolated from individuals with COPD.
Clifford RL and Fishbane N and Patel J and MacIsaac JL and McEwen LM and Fisher AJ and Brandsma CA and Nair P and Kobor MS and Hackett TL and Knox AJ
DNA methylation as a predictor of fetal alcohol spectrum disorder.
Lussier AA and Morin AM and MacIsaac JL and Salmon J and Weinberg J and Reynolds JN and Pavlidis P and Chudley AE and Kobor MS
Agreement in DNA methylation levels from the Illumina 450K array across batches, tissues, and time.
Forest M and O'Donnell KJ and Voisin G and Gaudreau H and MacIsaac JL and McEwen LM and Silveira PP and Steiner M and Kobor MS and Meaney MJ and Greenwood CMT
Epigenetic correlates of neonatal contact in humans.
Development and psychopathology
Moore SR and McEwen LM and Quirt J and Morin A and Mah SM and Barr RG and Boyce WT and Kobor MS
DNA methylation signatures of chronic alcohol dependence in purified CD3+ T-cells of patients undergoing alcohol treatment
Christof Brückmann and Sumaiya A. Islam and Julia L. MacIsaac and Alexander M. Morin and Kathrin N. Karle and Adriana Di Santo and Richard Wüst and Immanuel Lang and Anil Batra and Michael S. Kobor and Vanessa Nieratschker
Choice of surrogate tissue influences neonatal EWAS findings.
Lin X and Teh AL and Chen L and Lim IY and Tan PF and MacIsaac JL and Morin AM and Yap F and Tan KH and Saw SM and Lee YS and Holbrook JD and Godfrey KM and Meaney MJ and Kobor MS and Chong YS and Karnani N
Modes of Infant Feeding and the Risk of Childhood Asthma: A Prospective Birth Cohort Study.
The Journal of pediatrics
Klopp A and Vehling L and Becker AB and Subbarao P and Mandhane PJ and Turvey SE and Lefebvre DL and Sears MR and CHILD Study Investigators and Azad MB
PRS-on-Spark: a novel, efficient and flexible approach for generating polygenic risk scores
Chen LM and Yao N and Garg E and Zhu Y and Nguyen TTT and Pokhvisneva I and Hari Dass SA and Forest M and McEwen LM and MacIsaac JL and Kobor MS and Greenwood CMT and Silveira PP and O'Donnell KJ
Worldwide patterns of human epigenetic variation
Nature Ecology & Evolution
Oana Carja and Julia L. MacIsaac and Sarah M. Mah and Brenna M. Henn and Michael S. Kobor and Marcus W. Feldman and Hunter B. Fraser
Birth weight and postnatal microbial exposures predict the distribution of peripheral blood leukocyte subsets in young adults in the Philippines.
Journal of developmental origins of health and disease
DNA methylation patterns are related to co-morbidity status and circulating C-reactive protein levels in the nursing home elderly.
Timing of food introduction and development of food sensitization in a prospective birth cohort.
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology
Social and physical environments early in development predict DNA methylation of inflammatory genes in young adulthood.
Proceedings of the National Academy of Sciences of the United States of America
The Intersection Of Aging Biology and The Pathobiology of Lung Diseases: A Joint NHLBI/NIA Workshop.
Budinger GS and Kohanski RA and Gan W and Kobor MS and Amaral LA and Armanios M and Kelsey KT and Pardo A and Tuder R and Macian F and Chandel N and Vaughan D and Rojas M and Mora AL and Kovacs E and Duncan SR and Finkel T and Choi A and Eickelberg O and Chen D and dummy-AUTHOR_name and Thannickal VJ
Exposure to household furry pets influences the gut microbiota of infant at 3-4 months following various birth scenarios.
Tun HM and Konya T and Takaro TK and Brook JR and Chari R and Field CJ and Guttman DS and Becker AB and Mandhane PJ and Turvey SE and Subbarao P and Sears MR and Scott JA and Kozyrskyj AL and CHILD Study Investigators
Developmental pathways to adiposity begin before birth and are influenced by genotype, prenatal environment and epigenome.
Lin X and Lim IY and Wu Y and Teh AL and Chen L and Aris IM and Soh SE and Tint MT and MacIsaac JL and Morin AM and Yap F and Tan KH and Saw SM and Kobor MS and Meaney MJ and Godfrey KM and Chong YS and Holbrook JD and Lee YS and Gluckman PD
Longitudinal study of surrogate aging measures during human immunodeficiency virus seroconversion.
Leung JM and Fishbane N and Jones M and Morin A and Xu S and Liu JC and MacIsaac J and Milloy MJ and Hayashi K and Montaner J and Horvath S and Kobor M and Sin DD and Harrigan PR and Man SF
Inhalation of diesel exhaust and allergen alters human bronchial epithelium DNA methylation.
Clifford RL and Jones MJ and MacIsaac JL and McEwen LM and Goodman SJ and Mostafavi S and Kobor MS and Carlsten C
An empirically driven data reduction method on the human 450K methylation array to remove tissue specific non-variable CpGs.
Edgar RD and Jones MJ and Robinson WP and Kobor MS
Cesarean Section, Formula Feeding, and Infant Antibiotic Exposure: Separate and Combined Impacts on Gut Microbial Changes in Later Infancy.
Frontiers in Pediatrics
Associations between maternal risk factors of adverse pregnancy and birth outcomes and the offspring epigenetic clock of gestational age at birth.
Girchenko P and Lahti J and Czamara D and Knight AK and Jones MJ and Suarez A and Hämäläinen E and Kajantie E and Laivuori H and Villa PM and Reynolds RM and Kobor MS and Smith AK and Binder EB and Räikkönen K
Fecal Short-Chain Fatty Acid Variations by Breastfeeding Status in Infants at 4¿Months: Differences in Relative versus Absolute Concentrations.
Bridgman SL and Azad MB and Field CJ and Haqq AM and Becker AB and Mandhane PJ and Subbarao P and Turvey SE and Sears MR and Scott JA and Wishart DS and Kozyrskyj AL and CHILD Study Investigators
Differential DNA methylation and lymphocyte proportions in a Costa Rican high longevity region.
McEwen LM and Morin AM and Edgar RD and MacIsaac JL and Jones MJ and Dow WH and Rosero-Bixby L and Kobor MS and Rehkopf DH
Genome-wide Interaction Analysis of Air Pollution Exposure and Childhood Asthma with Functional Follow-up.
Gref A and Kebede Merid S and Gruzieva O and Ballereau S and Becker A and Bellander T and Bergström A and Bossé Y and Bottai M and Chan-Yeung M and Fuertes E and Ierodiakonou D and Jiang R and Joly S and Jones M and Kobor MS and Korek M and Kozyrskyj AL and Kumar A and Lemonnier N
Combined Action of Histone Reader Modules Regulates NuA4 Local Acetyltransferase Function but Not Its Recruitment on the Genome.
Steunou AL and Cramet M and Rossetto D and Aristizabal MJ and Lacoste N and Drouin S and Côté V and Paquet E and Utley RT and Krogan N and Robert F and Kobor MS and Côté J
An epigenetic clock analysis of race/ethnicity, sex, and coronary heart disease.
Horvath S and Gurven M and Levine ME and Trumble BC and Kaplan H and Allayee H and Ritz BR and Chen B and Lu AT and Rickabaugh TM and Jamieson BD and Sun D and Li S and Chen W and Quintana-Murci L and Fagny M and Kobor MS and Tsao PS and Reiner AP and Edlefsen KL
Low birth weight associates with hippocampal gene expression.
Buschdorf JP and Ong ML and Ong SX and MacIsaac JL and Chng K and Kobor MS and Meaney MJ and Holbrook JD
DNA Methylation Profiling in Human Huntington's Disease Brain.
De Souza RA and Islam SA and McEwen LM and Mathelier A and Hill A and Mah SM and Wasserman WW and Kobor MS and Leavitt BR
Differential DNA methylation in peripheral blood mononuclear cells in adolescents exposed to significant early but not later childhood adversity.
Esposito EA and Jones MJ and Doom JR and MacIsaac JL and Gunnar MR and Kobor MS
funtooNorm: an R package for normalization of DNA methylation data when there are multiple cell or tissue types.
Oros Klein K and Grinek S and Bernatsky S and Bouchard L and Ciampi A and Colmegna I and Fortin JP and Gao L and Hivert MF and Hudson M and Kobor MS and Labbe A and MacIsaac JL and Meaney MJ and Morin AM and O'Donnell KJ and Pastinen T and Van Ijzendoorn MH and Voisin G and Greenwood CM
Infant gut immunity: a preliminary study of IgA associations with breastfeeding.
Bridgman SL and Konya T and Azad MB and Sears MR and Becker AB and Turvey SE and Mandhane PJ and Subbarao P and CHILD Study Investigators and Scott JA and Field CJ and Kozyrskyj AL
Comparison of Methyl-capture Sequencing vs. Infinium 450K methylation array for methylome analysis in clinical samples.
Teh AL and Pan H and Lin X and Lim YI and Patro CP and Cheong CY and Gong M and MacIsaac JL and Kwoh CK and Meaney MJ and Kobor MS and Chong YS and Gluckman PD and Holbrook JD and Karnani N
Natural variation in maternal care and cross-tissue patterns of oxytocin receptor gene methylation in rats.
Beery AK and McEwen LM and MacIsaac JL and Francis DD and Kobor MS
Improving cell mixture deconvolution by identifying optimal DNA methylation libraries (IDOL).
Koestler DC and Jones MJ and Usset J and Christensen BC and Butler RA and Kobor MS and Wiencke JK and Kelsey KT
DNA methylation signature of human fetal alcohol spectrum disorder.
Portales-Casamar E and Lussier AA and Jones MJ and MacIsaac JL and Edgar RD and Mah SM and Barhdadi A and Provost S and Lemieux-Perreault LP and Cynader MS and Chudley AE and Dubé MP and Reynolds JN and Pavlidis P and Kobor MS
AllerGen’s 8th research conference.
Arrieta M and Arevalos A and Stiemsma L and Chico ME and Sandoval C and Jin M and Walter J and Cooper P and Finlay B and Bernatchez E and Gold MJ and Langlois A and Blais-Lecours P and Duchaine C and Marsolais D and McNagny KM and Blanchet M and Brubacher J and Chhetri B and Sabaliauskas K
Bacterial infection remodels the DNA methylation landscape of human dendritic cells.
Pacis A and Tailleux L and Morin AM and Lambourne J and MacIsaac JL and Yotova V and Dumaine A and Danckaert A and Luca F and Grenier JC and Hansen KD and Gicquel B and Yu M and Pai A and He C and Tung J and Pastinen T and Kobor MS and Pique-Regi R and Gilad Y
Maternal early life adversities and the offspring's epigenome: A M.A.V.A.N. project.
Unternaehrer E and O'Donnell K and Bouvette-Turcot AA and Gaudreau H and Cost K and Fleming A and Steiner M and MacIsaac J and Mah S and McEwen L and Kobor M and Chen L and Pan H and Hui WY and Holbrook J and Meaney M and Study Team MAVAN
The RNAPII-CTD Maintains Genome Integrity through Inhibition of Retrotransposon Gene Expression and Transposition.
Aristizabal MJ and Negri GL and Kobor MS
The Canadian Healthy Infant Longitudinal Development (CHILD) Study: examining developmental origins of allergy and asthma.
Subbarao P and Anand SS and Becker AB and Befus AD and Brauer M and Brook JR and Denburg JA and HayGlass KT and Kobor MS and Kollmann TR and Kozyrskyj AL and Lou WY and Mandhane PJ and Miller GE and Moraes TJ and Pare PD and Scott JA and Takaro TK and Turvey SE and Duncan JM
Impact of maternal intrapartum antibiotics, method of birth and breastfeeding on gut microbiota during the first year of life: a prospective cohort study.
Azad MB and Konya T and Persaud RR and Guttman DS and Chari RS and Field CJ and Sears MR and Mandhane PJ and Turvey SE and Subbarao P and Becker AB and Scott JA and Kozyrskyj AL and CHILD Study Investigators
Prenatal alcohol exposure alters gene expression in the rat brain: Experimental design and bioinformatic analysis of microarray data.
Lussier AA and Stepien KA and Weinberg J and Kobor MS
A pooling-based approach to mapping genetic variants associated with DNA methylation.
Kaplow IM and MacIsaac JL and Mah SM and McEwen LM and Kobor MS and Fraser HB
Landscape of DNA methylation on the X chromosome reflects CpG density, functional chromatin state and X-chromosome inactivation.
Cotton AM and Price EM and Jones MJ and Balaton BP and Kobor MS and Brown CJ
Infant gut microbiota and food sensitization: associations in the first year of life.
Azad MB and Konya T and Guttman DS and Field CJ and Sears MR and HayGlass KT and Mandhane PJ and Turvey SE and Subbarao P and Becker AB and Scott JA and Kozyrskyj AL and CHILD Study Investigators
Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism influences the association of the methylome with maternal anxiety and neonatal brain volumes.
Chen L and Pan H and Tuan TA and Teh AL and MacIsaac JL and Mah SM and McEwen LM and Li Y and Chen H and Broekman BF and Buschdorf JP and Chong YS and Kwek K and Saw SM and Gluckman PD and Fortier MV and Rifkin-Graboi A and Kobor MS and Qiu A and Meaney MJ
Prenatal alcohol exposure alters steady-state and activated gene expression in the adult rat brain.
Lussier AA and Stepien KA and Neumann SM and Pavlidis P and Kobor MS and Weinberg J
The Canadian healthy infant longitudinal development birth cohort study: biological samples and biobanking.
Moraes TJ and Lefebvre DL and Chooniedass R and Becker AB and Brook JR and Denburg J and HayGlass KT and Hegele RG and Kollmann TR and Macri J and Mandhane PJ and Scott JA and Subbarao P and Takaro TK and Turvey SE and Duncan JD and Sears MR and Befus AD and CHILD Study Investigators
The epigenomic landscape of African rainforest hunter-gatherers and farmers.
Fagny M and Patin E and MacIsaac JL and Rotival M and Flutre T and Jones MJ and Siddle KJ and Quach H and Harmant C and McEwen LM and Froment A and Heyer E and Gessain A and Betsem E and Mouguiama-Daouda P and Hombert JM and Perry GH and Barreiro LB and Kobor MS and Quintana-Murci L
Nucleated red blood cells impact DNA methylation and expression analyses of cord blood hematopoietic cells.
de Goede OM and Razzaghian HR and Price EM and Jones MJ and Kobor MS and Robinson WP and Lavoie PM
Concordant and discordant DNA methylation signatures of aging in human blood and brain.
Farré P and Jones MJ and Meaney MJ and Emberly E and Turecki G and Kobor MS
HIF3A association with adiposity: the story begins before birth.
Pan H and Lin X and Wu Y and Chen L and Teh AL and Soh SE and Lee YS and Tint MT and MacIsaac JL and Morin AM and Tan KH and Yap F and Saw SM and Kobor MS and Meaney MJ and Godfrey KM and Chong YS and Gluckman PD and Karnani N and Holbrook JD
Prenatal antidepressant exposure associated with CYP2E1 DNA methylation change in neonates.
Gurnot C and Martin-Subero I and Mah SM and Weikum W and Goodman SJ and Brain U and Werker JF and Kobor MS and Esteller M and Oberlander TF and Hensch TK
The Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort study: assessment of environmental exposures.
Takaro TK and Scott JA and Allen RW and Anand SS and Becker AB and Befus AD and Brauer M and Duncan J and Lefebvre DL and Lou W and Mandhane PJ and McLean KE and Miller G and Sbihi H and Shu H and Subbarao P and Turvey SE and Wheeler AJ and Zeng L and Sears MR
Discordance of DNA methylation variance between two accessible human tissues.
Jiang R and Jones MJ and Chen E and Neumann SM and Fraser HB and Miller GE and Kobor MS
Leishmania donovani infection causes distinct epigenetic DNA methylation changes in host macrophages.
Marr AK and MacIsaac JL and Jiang R and Airo AM and Kobor MS and McMaster WR
Greater inflammatory activity and blunted glucocorticoid signaling in monocytes of chronically stressed caregivers.
Miller GE and Murphy ML and Cashman R and Ma R and Ma J and Arevalo JM and Kobor MS and Cole SW
Infinium monkeys: Infinium 450K array for the Cynomolgus macaque (Macaca fascicularis).
Ong ML and Tan PY and MacIsaac JL and Mah SM and Buschdorf JP and Cheong CY and Stunkel W and Chan L and Gluckman PD and Chng K and Kobor MS and Meaney MJ and Holbrook JD
The effect of genotype and in utero environment on interindividual variation in neonate DNA methylomes.
Teh AL and Pan H and Chen L and Ong ML and Dogra S and Wong J and MacIsaac JL and Mah SM and McEwen LM and Saw SM and Godfrey KM and Chong YS and Kwek K and Kwoh CK and Soh SE and Chong MF and Barton S and Karnani N and Cheong CY and Buschdorf JP
Eaf5/7/3 form a functionally independent NuA4 submodule linked to RNA polymerase II-coupled nucleosome recycling.
Rossetto D and Cramet M and Wang AY and Steunou AL and Lacoste N and Schulze JM and Côté V and Monnet-Saksouk J and Piquet S and Nourani A and Kobor MS and Côté J
Conditional genetic interactions of RTT107, SLX4, and HRQ1 reveal dynamic networks upon DNA damage in S. cerevisiae.
Leung GP and Aristizabal MJ and Krogan NJ and Kobor MS
Associations between bacterial communities of house dust and infant gut.
Konya T and Koster B and Maughan H and Escobar M and Azad MB and Guttman DS and Sears MR and Becker AB and Brook JR and Takaro TK and Kozyrskyj AL and Scott JA and CHILD Study Investigators
Maintenance of heterochromatin boundary and nucleosome composition at promoters by the Asf1 histone chaperone and SWR1-C chromatin remodeler in Saccharomyces cerevisiae.
Lu PY and Kobor MS
Genome-wide profiling of yeast DNA:RNA hybrid prone sites with DRIP-chip.
Chan YA and Aristizabal MJ and Lu PY and Luo Z and Hamza A and Kobor MS and Stirling PC and Hieter P
Spread of X-chromosome inactivation into autosomal sequences: role for DNA elements, chromatin features and chromosomal domains.
Cotton AM and Chen CY and Lam LL and Wasserman WW and Kobor MS and Brown CJ
Short-term diesel exhaust inhalation in a controlled human crossover study is associated with changes in DNA methylation of circulating mononuclear cells in asthmatics.
Jiang R and Jones MJ and Sava F and Kobor MS and Carlsten C
Molecular pathways underpinning ethanol-induced neurodegeneration.
Goldowitz D and Lussier AA and Boyle JK and Wong K and Lattimer SL and Dubose C and Lu L and Kobor MS and Hamre KM
Genomewide DNA methylation dynamics upon diesel exhaust exposure in asthmatics.
Jiang R and Sava F and Kobor MS and Carlsten CR
Social stress up-regulates inflammatory gene expression in the leukocyte transcriptome via ß-adrenergic induction of myelopoiesis.
Powell ND and Sloan EK and Bailey MT and Arevalo JM and Miller GE and Chen E and Kobor MS and Reader BF and Sheridan JF and Cole SW
High-throughput genetic and gene expression analysis of the RNAPII-CTD reveals unexpected connections to SRB10/CDK8.
Aristizabal MJ and Negri GL and Benschop JJ and Holstege FC and Krogan NJ and Kobor MS
Reply to Suderman et al.: Importance of accounting for blood cell composition in epigenetic studies.
Lam LL and Emberly E and Fraser HB and Neumann SM and Chen E and Miller GE and Kobor MS
Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months.
Azad MB and Konya T and Maughan H and Guttman DS and Field CJ and Chari RS and Sears MR and Becker AB and Scott JA and Kozyrskyj AL and CHILD Study Investigators
Distinct DNA methylation patterns of cognitive impairment and trisomy 21 in Down syndrome.
Jones MJ and Farré P and McEwen LM and Macisaac JL and Watt K and Neumann SM and Emberly E and Cynader MS and Virji-Babul N and Kobor MS
Epigenetic vestiges of early developmental adversity: childhood stress exposure and DNA methylation in adolescence.
Essex MJ and Boyce WT and Hertzman C and Lam LL and Armstrong JM and Neumann SM and Kobor MS
The molecular mechanism of a cis-regulatory adaptation in yeast.
Chang J and Zhou Y and Hu X and Lam L and Henry C and Green EM and Kita R and Kobor MS and Fraser HB
Additional annotation enhances potential for biologically-relevant analysis of the Illumina Infinium HumanMethylation450 BeadChip array.
Price ME and Cotton AM and Lam LL and Farré P and Emberly E and Brown CJ and Robinson WP and Kobor MS
Histone H3K4 demethylation is negatively regulated by histone H3 acetylation in Saccharomyces cerevisiae.
Maltby VE and Martin BJ and Brind'Amour J and Chruscicki AT and McBurney KL and Schulze JM and Johnson IJ and Hills M and Hentrich T and Kobor MS and Lorincz MC and Howe LJ
Factors underlying variable DNA methylation in a human community cohort.
Lam LL and Emberly E and Fraser HB and Neumann SM and Chen E and Miller GE and Kobor MS
Histone H3 lysine 36 methylation targets the Isw1b remodeling complex to chromatin.
Maltby VE and Martin BJ and Schulze JM and Johnson I and Hentrich T and Sharma A and Kobor MS and Howe L
p300/CBP-associated factor selectively regulates the extinction of conditioned fear.
Wei W and Coelho CM and Li X and Marek R and Yan S and Anderson S and Meyers D and Mukherjee C and Sbardella G and Castellano S and Milite C and Rotili D and Mai A and Cole PA and Sah P and Kobor MS and Bredy TW
Different measures of "genome-wide" DNA methylation exhibit unique properties in placental and somatic tissues.
Price EM and Cotton AM and Peñaherrera MS and McFadden DE and Kobor MS and Robinson W
R-loop-mediated genome instability in mRNA cleavage and polyadenylation mutants.
Stirling PC and Chan YA and Minaker SW and Aristizabal MJ and Barrett I and Sipahimalani P and Kobor MS and Hieter P
19p13.2 microduplication causes a Sotos syndrome-like phenotype and alters gene expression.
Lehman AM and du Souich C and Chai D and Eydoux P and Huang JL and Fok AK and Avila L and Swingland J and Delaney AD and McGillivray B and Goldowitz D and Argiropoulos B and Kobor MS and Boerkoel CF
DNA methylation profiles of airway epithelial cells and PBMCs from healthy, atopic and asthmatic children.
Stefanowicz D and Hackett TL and Garmaroudi FS and Günther OP and Neumann S and Sutanto EN and Ling KM and Kobor MS and Kicic A and Stick SM and Paré PD and Knight DA
Splitting the task: Ubp8 and Ubp10 deubiquitinate different cellular pools of H2BK123.
Schulze JM and Hentrich T and Nakanishi S and Gupta A and Emberly E and Shilatifard A and Kobor MS
The brain-specific microRNA miR-128b regulates the formation of fear-extinction memory.
Lin Q and Wei W and Coelho CM and Li X and Baker-Andresen D and Dudley K and Ratnu VS and Boskovic Z and Kobor MS and Sun YE and Bredy TW
Chromosome-wide DNA methylation analysis predicts human tissue-specific X inactivation.
Cotton AM and Lam L and Affleck JG and Wilson IM and Peñaherrera MS and McFadden DE and Kobor MS and Lam WL and Robinson WP and Brown CJ
Maternal warmth buffers the effects of low early-life socioeconomic status on pro-inflammatory signaling in adulthood.
Chen E and Miller GE and Kobor MS and Cole SW
Epigenetic mechanisms mediating vulnerability and resilience to psychiatric disorders.
Dudley KJ and Li X and Kobor MS and Kippin TE and Bredy TW
The specificity and topology of chromatin interaction pathways in yeast.
Lenstra TL and Benschop JJ and Kim T and Schulze JM and Brabers NA and Margaritis T and van de Pasch LA and van Heesch SA and Brok MO and Groot Koerkamp MJ and Ko CW and van Leenen D and Sameith K and van Hooff SR and Lijnzaad P and Kemmeren P and Hentrich T and Kobor MS and Buratowski S and Holstege FC
Dot1 and histone H3K79 methylation in natural telomeric and HM silencing.
Takahashi YH and Schulze JM and Jackson J and Hentrich T and Seidel C and Jaspersen SL and Kobor MS and Shilatifard A
Fetal alcohol spectrum disorders: gene-environment interactions, predictive biomarkers, and the relationship between structural alterations in the brain and functional outcomes.
Reynolds JN and Weinberg J and Clarren S and Beaulieu C and Rasmussen C and Kobor M and Dube MP and Goldowitz D
Extensive epigenetic reprogramming in human somatic tissues between fetus and adult.
Yuen RK and Neumann SM and Fok AK and Peñaherrera MS and McFadden DE and Robinson WP and Kobor MS
Focus on: epigenetics and fetal alcohol spectrum disorders.
Kobor MS and Weinberg J
Loss of H3 K79 trimethylation leads to suppression of Rtt107-dependent DNA damage sensitivity through the translesion synthesis pathway.
Lévesque N and Leung GP and Fok AK and Schmidt TI and Kobor MS
Decreased fibronectin production significantly contributes to dysregulated repair of asthmatic epithelium.
Kicic A and Hallstrand TS and Sutanto EN and Stevens PT and Kobor MS and Taplin C and Paré PD and Beyer RP and Stick SM and Knight DA
Roles for H2A.Z and its acetylation in GAL1 transcription and gene induction, but not GAL1-transcriptional memory.
Halley JE and Kaplan T and Wang AY and Kobor MS and Rine J
Asf1-like structure of the conserved Yaf9 YEATS domain and role in H2A.Z deposition and acetylation.
Wang AY and Schulze JM and Skordalakes E and Gin JW and Berger JM and Rine J and Kobor MS
Linking cell cycle to histone modifications: SBF and H2B monoubiquitination machinery and cell-cycle regulation of H3K79 dimethylation.
Schulze JM and Jackson J and Nakanishi S and Gardner JM and Hentrich T and Haug J and Johnston M and Jaspersen SL and Kobor MS and Shilatifard A
Low early-life social class leaves a biological residue manifested by decreased glucocorticoid and increased proinflammatory signaling.
Miller GE and Chen E and Fok AK and Walker H and Lim A and Nicholls EF and Cole S and Kobor MS
Human placental-specific epipolymorphism and its association with adverse pregnancy outcomes.
Yuen RK and Avila L and Peñaherrera MS and von Dadelszen P and Lefebvre L and Kobor MS and Robinson WP
Slx4 regulates DNA damage checkpoint-dependent phosphorylation of the BRCT domain protein Rtt107/Esc4.
Roberts TM and Kobor MS and Bastin-Shanower SA and Ii M and Horte SA and Gin JW and Emili A and Rine J and Brill SJ and Brown GW
NMR structure of the amino-terminal domain from the Tfb1 subunit of TFIIH and characterization of its phosphoinositide and VP16 binding sites.
Di Lello P and Nguyen BD and Jones TN and Potempa K and Kobor MS and Legault P and Omichinski JG
Interaction of Fcp1 phosphatase with elongating RNA polymerase II holoenzyme, enzymatic mechanism of action, and genetic interaction with elongator.
Kong SE and Kobor MS and Krogan NJ and Somesh BP and Søgaard TM and Greenblatt JF and Svejstrup JQ
Dephosphorylation of RNA polymerase I by Fcp1p is required for efficient rRNA synthesis.
Fath S and Kobor MS and Philippi A and Greenblatt J and Tschochner H
A protein complex containing the conserved Swi2/Snf2-related ATPase Swr1p deposits histone variant H2A.Z into euchromatin.
Kobor MS and Venkatasubrahmanyam S and Meneghini MD and Gin JW and Jennings JL and Link AJ and Madhani HD and Rine J
NMR structure of a complex containing the TFIIF subunit RAP74 and the RNA polymerase II carboxyl-terminal domain phosphatase FCP1.
Nguyen BD and Abbott KL and Potempa K and Kobor MS and Archambault J and Greenblatt J and Legault P and Omichinski JG
Solution structure of the carboxyl-terminal domain of RAP74 and NMR characterization of the FCP1-binding sites of RAP74 and human TFIIB.
Nguyen BD and Chen HT and Kobor MS and Greenblatt J and Legault P and Omichinski JG
Purification and assay of Saccharomyces cerevisiae phosphatase that acts on the C-terminal domain of the largest subunit of RNA polymerase II.
Hoheisel S and Kobor MS and Pierstorff E and Greenblatt J and Kane CM
RNA polymerase II elongation factors of Saccharomyces cerevisiae: a targeted proteomics approach.
Krogan NJ and Kim M and Ahn SH and Zhong G and Kobor MS and Cagney G and Emili A and Shilatifard A and Buratowski S and Greenblatt JF
Opposing effects of Ctk1 kinase and Fcp1 phosphatase at Ser 2 of the RNA polymerase II C-terminal domain.
Cho EJ and Kobor MS and Kim M and Greenblatt J and Buratowski S
A motif shared by TFIIF and TFIIB mediates their interaction with the RNA polymerase II carboxy-terminal domain phosphatase Fcp1p in Saccharomyces cerevisiae.
Kobor MS and Simon LD and Omichinski J and Zhong G and Archambault J and Greenblatt J
An unusual eukaryotic protein phosphatase required for transcription by RNA polymerase II and CTD dephosphorylation in S. cerevisiae.
Kobor MS and Archambault J and Lester W and Holstege FC and Gileadi O and Jansma DB and Jennings EG and Kouyoumdjian F and Davidson AR and Young RA and Greenblatt J
GAL4 is regulated by the RNA polymerase II holoenzyme-associated cyclin-dependent protein kinase SRB10/CDK8.
Hirst M and Kobor MS and Kuriakose N and Greenblatt J and Sadowski I
An essential component of a C-terminal domain phosphatase that interacts with transcription factor IIF in Saccharomyces cerevisiae.
Archambault J and Chambers RS and Kobor MS and Ho Y and Cartier M and Bolotin D and Andrews B and Kane CM and Greenblatt J
Identification of a nucleic acid-binding region within the largest subunit of Drosophila melanogaster RNA polymerase II.
Kontermann RE and Kobor M and Bautz EK
In one facet of our research program, we study human population epigenetics aimed at deciphering the mechanisms by which environmental exposures and early-life experiences can "get under the skin" to regulate gene activity and contribute to health and disease across the life course. This research aligns with the Developmental Origins of Health and Disease (DOHaD) hypothesis, which postulates that the developmental period and early life are particularly sensitive periods where social or environmental insults can influence health long after the insult itself. Our findings support the model that early-life social and environmental factors, including stress and socioeconomic status, leave a biological footprint. We measure this biological embedding of early life exposures through epigenetic patterns and accompanying gene expression changes, many of which are maintained until adulthood and may influence future health. We have extensive interdisciplinary collaborations across Canada and around the world and are affiliated with multiple NCEs (including AllerGen and NeuroDevNet).
Rather than acting as an inert scaffold for DNA, dynamic and flexible chromatin structures and modifications have profound effects on almost all aspects of chromosome behaviour and genome function. Thus, the second objective of our research utilizes Saccharomyces cerevisiae as a model organism to tease apart the mechanisms responsible for the creation, regulation, and maintenance of the chromatin signature. These queries include how distinct chromosomal neighbourhoods are established, how they function and interact with enzymes involved in DNA metabolism, what functional differences exist between histone variants and canonical histones, and how chromatin-remodeling complexes are regulated. Currently, we focus on three distinct areas of chromatin biology: functional genomic characterization of chromatin-modifying complexes; DNA damage repair in the context of the chromatin template; and crosstalk between the RNAPII machinery and chromatin.
Together, the research in our lab bridges the molecular mechanisms of epigenetic regulation with the social and environmental determinants of human health to develop a comprehensive understanding of early life.Honours & Awards
Award of Excellence, Biomedical Research, CFRI Member Recognition Awards, 2013
Canada Research Chair Tier 1 in Social Epigenetics, 2014-present
Senior Fellow, Canadian Institute for Advanced Research, Child & Brain Development program, 2013-presentResearch Group Members
Neeku Amanat, Co-op Student
Paola Arguello-Pascualli, Master student
Maria Aristizabal, Postdoctoral Fellow
Rebecca Asiimwe, Bioinformatician
Parmida Atashzay, Research Assistant
Sanjit Bains, Research Assistant
Helena Brendler, PhD student
Josh Brown, Doctoral Student
Yen Chan, Graduate Student
Joe Dong, Graduate Research Assistant
Cath Ennis, Knowledge Translation Specialist
Tanya Erb, Research Manager
Maggie Fu, Graduate Student
Kiara Gibbons, Research Coordinator
Analisa Jia, Volunteer
Pareesa Kassam, Directed Studies Student
Chaini Konwar, Doctoral Student
David Lin, PhD Research Associate
Julie MacIsaac, Research Associate/Lab manager
Quinn McVeigh, Research Assistant
Sarah Merrill, Postdoctoral Research Fellow:
Sarah Moore, Postdoctoral Fellow
Alexander Morin, Graduate Research Asst
Taylor Morrison, Volunteer Undergraduate Assistant
Lindy Moxham, Co-op Student
Sharlin Patel, Research Assistant
Katia Ramadori, Research Technician
Tiffany Reeve, Healthy Starts Strategic Initiatives Manager
Samantha Schaffner, Graduate Research Assistant
Nivretta Thatra, Graduate Student
Stephanie Thompson, Visiting International Student
Joanne Whitehead, Bioinformatician
Ariane Wiegand, Visiting Researcher