title: Identification of genetic variants that affect histone modifications in human cells.
abstract: Histone modifications are important markers of function and chromatin state, yet the DNA sequence elements that direct them to specific genomic locations are poorly understood. Here, we identify hundreds of quantitative trait loci, genome-wide, that affect histone modification or RNA polymerase II (Pol II) occupancy in Yoruba lymphoblastoid cell lines (LCLs). In many cases, the same variant is associated with quantitative changes in multiple histone marks and Pol II, as well as in deoxyribonuclease I sensitivity and nucleosome positioning. Transcription factor binding site polymorphisms are correlated overall with differences in local histone modification, and we identify specific transcription factors whose binding leads to histone modification in LCLs. Furthermore, variants that affect chromatin at distal regulatory sites frequently also direct changes in chromatin and gene expression at associated promoters.
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Graham
authors.initials: G
authors.lastname: McVicker
authors.forename: Bryce
authors.initials: B
authors.lastname: van de Geijn
authors.forename: Jacob F
authors.initials: JF
authors.lastname: Degner
authors.forename: Carolyn E
authors.initials: CE
authors.lastname: Cain
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Banovich
authors.forename: Anil
authors.initials: A
authors.lastname: Raj
authors.forename: Noah
authors.initials: N
authors.lastname: Lewellen
authors.forename: Marsha
authors.initials: M
authors.lastname: Myrthil
authors.forename: Yoav
authors.initials: Y
authors.lastname: Gilad
authors.forename: Jonathan K
authors.initials: JK
authors.lastname: Pritchard
mesh_terms: D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D002477:Cells / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D014644:Genetic Variation; D015894:Genome, Human; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D040641:Quantitative Trait Loci; D012319:RNA Polymerase II / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D006657:Histones; D014157:Transcription Factors; D012319:RNA Polymerase II