期刊
CELL
卷 162, 期 5, 页码 1039-1050出版社
CELL PRESS
DOI: 10.1016/j.cell.2015.08.001
关键词
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资金
- Swiss National Science Foundation [CRSI33_130326, 31003A_132958, 31003A_130342, 149984, 31003A_129835, 31003A_138323]
- European Research Council
- Louis-Jeantet Foundation
- SystemsX grant [3826]
- NIH [MH101814]
- European Molecular Biology Organization fellowship [ALTF 2010-337]
- doctoral school of the Faculty of Biology and Medicine, University of Lausanne
- NCCR Frontiers in Genetics Program
- Japanese-Swiss Science and Technology Cooperation Program (Japan Science and Technology Agency/ETH Zurich)
- Ecole Polytechnique Federale de Lausanne
- Swiss National Science Foundation (SNF) [CRSI33_130326, 31003A_130342, 31003A_132958, 31003A_138323, 31003A_129835] Funding Source: Swiss National Science Foundation (SNF)
Chromatin state variation at gene regulatory elements is abundant across individuals, yet we understand little about the genetic basis of this variability. Here, we profiled several histone modifications, the transcription factor (TF) PU.1, RNA polymerase II, and gene expression in lymphoblastoid cell lines from 47 whole-genome sequenced individuals. We observed that distinct cis-regulatory elements exhibit coordinated chromatin variation across individuals in the form of variable chromatin modules (VCMs) at sub-Mb scale. VCMs were associated with thousands of genes and preferentially cluster within chromosomal contact domains. We mapped strong proximal and weak, yet more ubiquitous, distal-acting chromatin quantitative trait loci (cQTL) that frequently explain this variation. cQTLs were associated with molecular activity at clusters of cis-regulatory elements and mapped preferentially within TF-bound regions. We propose that local, sequence-independent chromatin variation emerges as a result of genetic perturbations in cooperative interactions between cis-regulatory elements that are located within the same genomic domain.
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