title: Extensive variation in chromatin states across humans.
abstract: The majority of disease-associated variants lie outside protein-coding regions, suggesting a link between variation in regulatory regions and disease predisposition. We studied differences in chromatin states using five histone modifications, cohesin, and CTCF in lymphoblastoid lines from 19 individuals of diverse ancestry. We found extensive signal variation in regulatory regions, which often switch between active and repressed states across individuals. Enhancer activity is particularly diverse among individuals, whereas gene expression remains relatively stable. Chromatin variability shows genetic inheritance in trios, correlates with genetic variation and population divergence, and is associated with disruptions of transcription factor binding motifs. Overall, our results provide insights into chromatin variation among humans.
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Maya
authors.initials: M
authors.lastname: Kasowski
authors.forename: Sofia
authors.initials: S
authors.lastname: Kyriazopoulou-Panagiotopoulou
authors.forename: Fabian
authors.initials: F
authors.lastname: Grubert
authors.forename: Judith B
authors.initials: JB
authors.lastname: Zaugg
authors.forename: Anshul
authors.initials: A
authors.lastname: Kundaje
authors.forename: Yuling
authors.initials: Y
authors.lastname: Liu
authors.forename: Alan P
authors.initials: AP
authors.lastname: Boyle
authors.forename: Qiangfeng Cliff
authors.initials: QC
authors.lastname: Zhang
authors.forename: Fouad
authors.initials: F
authors.lastname: Zakharia
authors.forename: Damek V
authors.initials: DV
authors.lastname: Spacek
authors.forename: Jingjing
authors.initials: J
authors.lastname: Li
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
authors.forename: Anthony
authors.initials: A
authors.lastname: Olarerin-George
authors.forename: Lars M
authors.initials: LM
authors.lastname: Steinmetz
authors.forename: John B
authors.initials: JB
authors.lastname: Hogenesch
authors.forename: Manolis
authors.initials: M
authors.lastname: Kellis
authors.forename: Serafim
authors.initials: S
authors.lastname: Batzoglou
authors.forename: Michael
authors.initials: M
authors.lastname: Snyder
mesh_terms: D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000097722:Cohesins
chemical_list: D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D012097:Repressor Proteins; D014157:Transcription Factors; D000097722:Cohesins; C000619697:CTCF protein, human