title: Coordinated effects of sequence variation on DNA binding, chromatin structure, and transcription.
abstract: DNA sequence variation has been associated with quantitative changes in molecular phenotypes such as gene expression, but its impact on chromatin states is poorly characterized. To understand the interplay between chromatin and genetic control of gene regulation, we quantified allelic variability in transcription factor binding, histone modifications, and gene expression within humans. We found abundant allelic specificity in chromatin and extensive local, short-range, and long-range allelic coordination among the studied molecular phenotypes. We observed genetic influence on most of these phenotypes, with histone modifications exhibiting strong context-dependent behavior. Our results implicate transcription factors as primary mediators of sequence-specific regulation of gene expression programs, with histone modifications frequently reflecting the primary regulatory event.
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland.
authors.forename: Helena
authors.initials: H
authors.lastname: Kilpinen
authors.forename: Sebastian M
authors.initials: SM
authors.lastname: Waszak
authors.forename: Andreas R
authors.initials: AR
authors.lastname: Gschwind
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Raghav
authors.forename: Robert M
authors.initials: RM
authors.lastname: Witwicki
authors.forename: Andrea
authors.initials: A
authors.lastname: Orioli
authors.forename: Eugenia
authors.initials: E
authors.lastname: Migliavacca
authors.forename: Michaël
authors.initials: M
authors.lastname: Wiederkehr
authors.forename: Maria
authors.initials: M
authors.lastname: Gutierrez-Arcelus
authors.forename: Nikolaos I
authors.initials: NI
authors.lastname: Panousis
authors.forename: Alisa
authors.initials: A
authors.lastname: Yurovsky
authors.forename: Tuuli
authors.initials: T
authors.lastname: Lappalainen
authors.forename: Luciana
authors.initials: L
authors.lastname: Romano-Palumbo
authors.forename: Alexandra
authors.initials: A
authors.lastname: Planchon
authors.forename: Deborah
authors.initials: D
authors.lastname: Bielser
authors.forename: Julien
authors.initials: J
authors.lastname: Bryois
authors.forename: Ismael
authors.initials: I
authors.lastname: Padioleau
authors.forename: Gilles
authors.initials: G
authors.lastname: Udin
authors.forename: Sarah
authors.initials: S
authors.lastname: Thurnheer
authors.forename: David
authors.initials: D
authors.lastname: Hacker
authors.forename: Leighton J
authors.initials: LJ
authors.lastname: Core
authors.forename: John T
authors.initials: JT
authors.lastname: Lis
authors.forename: Nouria
authors.initials: N
authors.lastname: Hernandez
authors.forename: Alexandre
authors.initials: A
authors.lastname: Reymond
authors.forename: Bart
authors.initials: B
authors.lastname: Deplancke
authors.forename: Emmanouil T
authors.initials: ET
authors.lastname: Dermitzakis
mesh_terms: D000483:Alleles; D001483:Base Sequence / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation; D014644:Genetic Variation; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D006657:Histones; D014157:Transcription Factors; D004247:DNA