Oct 19, 2013

Identification of genetic variants that affect histone modifications in human cells

Science
Graham McVickerJonathan K Pritchard

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.

  • References40
  • Citations153

Mentioned in this Paper

RNA Polymerase II
Quantitative Trait Loci
Histone antigen
Deoxyribonuclease I
Genome
Post-Translational Protein Processing
Promoter
Gene Expression
Genomics
Histone Modification

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