Population Variation and Genetic Control of Modular Chromatin Architecture in Humans | Zendy

Sebastian M. Waszak | Zendy; Olivier Delaneau | Zendy; Andreas R. Gschwind | Zendy; Helena Kilpinen | Zendy; Sunil K. Raghav | Zendy; Robert M. Witwicki | Zendy; Andrea Orioli | Zendy; Michael R. Wiederkehr | Zendy; Nikolaos Panousis | Zendy; Alisa Yurovsky | Zendy; Luciana Romano-Palumbo | Zendy; Alexandra Planchon | Zendy; Deborah Bielser | Zendy; Ismaël Padioleau | Zendy; Gilles Udin | Zendy; Sarah Thurnheer | Zendy; David L. Hacker | Zendy; Nouria Hernandez | Zendy; Alexandre Reymond | Zendy; Bart Deplancke | Zendy; Emmanouil T. Dermitzakis | Zendy

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Population Variation and Genetic Control of Modular Chromatin Architecture in Humans

Author(s) -

Sebastian M. Waszak,

Olivier Delaneau,

Andreas R. Gschwind,

Helena Kilpinen,

Sunil K. Raghav,

Robert M. Witwicki,

Andrea Orioli,

Michael R. Wiederkehr,

Nikolaos Panousis,

Alisa Yurovsky,

Luciana Romano-Palumbo,

Alexandra Planchon,

Deborah Bielser,

Ismaël Padioleau,

Gilles Udin,

Sarah Thurnheer,

David L. Hacker,

Nouria Hernandez,

Alexandre Reymond,

Bart Deplancke,

Emmanouil T. Dermitzakis

Publication year - 2015

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2015.08.001

Subject(s) - biology , chromatin , genetics , chia pet , histone , gene , bivalent chromatin , chromatin remodeling , regulation of gene expression , genetic variation , transcription factor , population , computational biology , demography , sociology

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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