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Title

Population Variation and Genetic Control of Modular Chromatin Architecture in Humans

Authors
Waszak, Sebastian M
Gschwind, Andreas R
Raghav, Sunil K
Witwicki, Robert M
Orioli, Andrea
Wiederkehr, Michael
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Published in Cell. 2015, vol. 162, no. 5, p. 1039-1050
Abstract 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.
Keywords Chromatin/chemistry/metabolismChromosomes, Human/chemistryGene Expression RegulationGenetic VariationGenetics, PopulationGenome, HumanHumansQuantitative Trait LociRegulatory Sequences, Nucleic AcidTranscription Factors/metabolism
Identifiers
PMID: 26300124
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Structures
Research group Population Genomics and Genetics of Complex Traits (892)
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WASZAK, Sebastian M et al. Population Variation and Genetic Control of Modular Chromatin Architecture in Humans. In: Cell, 2015, vol. 162, n° 5, p. 1039-1050. doi: 10.1016/j.cell.2015.08.001 https://archive-ouverte.unige.ch/unige:89657

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Deposited on : 2016-11-30

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