Identification of genetic variants that affect histone modifications in human cells.
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ABSTRACT:
SUBMITTER: McVicker G
PROVIDER: S-EPMC3947669 | biostudies-literature | 2013 Nov
REPOSITORIES: biostudies-literature
Publications
Identification of genetic variants that affect histone modifications in human cells.
McVicker Graham G van de Geijn Bryce B Degner Jacob F JF Cain Carolyn E CE Banovich Nicholas E NE Raj Anil A Lewellen Noah N Myrthil Marsha M Gilad Yoav Y Pritchard Jonathan K JK
Science (New York, N.Y.) 20131017 6159
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 deoxyribonucle ...[more]
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Project description:Histone modifications are important markers of function and chromatin state, yet the DNA elements that direct them to specific locations in the genome are poorly understood. Here we use the genetic variation in Yoruba lymphoblastoid cell lines as a natural experiment to identify genetic differences that affect histone marks and to better understand their relationship with transcriptional regulation. Across the genome, we identified hundreds of quantitative trait loci that impact histone modification or RNA polymerase (PolII) occupancy. In many cases the same variant is associated with quantitative changes in multiple histone marks and PolII, as well as in DNaseI sensitivity and nucleosome positioning, indicating that these molecular phenotypes often share a single underlying genetic cause. Variants that impact chromatin at distal regulatory sites frequently also direct changes in chromatin and gene expression at associated promoters; while most of these distal regulators enhance promoter activity, some act as distal chromatin silencers. Finally, we find that polymorphisms in transcription factor binding sites are often causally responsible for variation in local histone modification. In summary, the class of variants identified here generate coordinated changes in chromatin both locally and sometimes at distant locations, frequently drive changes in gene expression, and likely play an important role in the genetics of complex traits. ChIP-seq of RNA Polymerase II and 4 histone modifications (H3K4me1, H3K4me3, H3K27ac, H3K27me3) in 10 unrelated Yoruba HapMap lymphoblastoid cell lines
2013-10-01 | E-GEOD-47991 | biostudies-arrayexpress
Project description:Histone modifications are important markers of function and chromatin state, yet the DNA elements that direct them to specific locations in the genome are poorly understood. Here we use the genetic variation in Yoruba lymphoblastoid cell lines as a natural experiment to identify genetic differences that affect histone marks and to better understand their relationship with transcriptional regulation. Across the genome, we identified hundreds of quantitative trait loci that impact histone modification or RNA polymerase (PolII) occupancy. In many cases the same variant is associated with quantitative changes in multiple histone marks and PolII, as well as in DNaseI sensitivity and nucleosome positioning, indicating that these molecular phenotypes often share a single underlying genetic cause. Variants that impact chromatin at distal regulatory sites frequently also direct changes in chromatin and gene expression at associated promoters; while most of these distal regulators enhance promoter activity, some act as distal chromatin silencers. Finally, we find that polymorphisms in transcription factor binding sites are often causally responsible for variation in local histone modification. In summary, the class of variants identified here generate coordinated changes in chromatin both locally and sometimes at distant locations, frequently drive changes in gene expression, and likely play an important role in the genetics of complex traits.
2013-10-01 | GSE47991 | GEO
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