Population Variation and Genetic Control of Modular Chromatin Architecture in Humans

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

doi:10.1016/j.cell.2015.08.001

Population Variation and Genetic Control of Modular Chromatin Architecture in Humans

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

Emmanouil T. Dermitzakis

Biomedical Informatics

Stony Brook University

Swiss Federal Institute of Technology Lausanne
Swiss Institute of Bioinformatics
European Molecular Biology Laboratory
University of Geneva
University of Lausanne

Research output: Contribution to journal › Article › peer-review

177 Scopus citations

Abstract

Summary 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.

Original language	English
Pages (from-to)	1039-1050
Number of pages	12
Journal	Cell
Volume	162
Issue number	5
DOIs	https://doi.org/10.1016/j.cell.2015.08.001
State	Published - Aug 27 2015

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Waszak, S. M., Delaneau, O., Gschwind, A. R., Kilpinen, H., Raghav, S. K., Witwicki, R. M., Orioli, A., Wiederkehr, M., Panousis, N. I., Yurovsky, A., Romano-Palumbo, L., Planchon, A., Bielser, D., Padioleau, I., Udin, G., Thurnheer, S., Hacker, D., Hernandez, N., Reymond, A., ... Dermitzakis, E. T. (2015). Population Variation and Genetic Control of Modular Chromatin Architecture in Humans. Cell, 162(5), 1039-1050. https://doi.org/10.1016/j.cell.2015.08.001

@article{bcbe6fd4245643228d5a3ea2cb447e81,

title = "Population Variation and Genetic Control of Modular Chromatin Architecture in Humans",

abstract = "Summary 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.",

author = "Waszak, \{Sebastian M.\} and Olivier Delaneau and Gschwind, \{Andreas R.\} and Helena Kilpinen and Raghav, \{Sunil K.\} and Witwicki, \{Robert M.\} and Andrea Orioli and Michael Wiederkehr and Panousis, \{Nikolaos I.\} and Alisa Yurovsky and Luciana Romano-Palumbo and Alexandra Planchon and Deborah Bielser and Ismael Padioleau and Gilles Udin and Sarah Thurnheer and David Hacker and Nouria Hernandez and Alexandre Reymond and Bart Deplancke and Dermitzakis, \{Emmanouil T.\}",

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

year = "2015",

month = aug,

day = "27",

doi = "10.1016/j.cell.2015.08.001",

language = "English",

volume = "162",

pages = "1039--1050",

journal = "Cell",

issn = "0092-8674",

number = "5",

}

Waszak, SM, Delaneau, O, Gschwind, AR, Kilpinen, H, Raghav, SK, Witwicki, RM, Orioli, A, Wiederkehr, M, Panousis, NI, Yurovsky, A, Romano-Palumbo, L, Planchon, A, Bielser, D, Padioleau, I, Udin, G, Thurnheer, S, Hacker, D, Hernandez, N, Reymond, A, Deplancke, B & Dermitzakis, ET 2015, 'Population Variation and Genetic Control of Modular Chromatin Architecture in Humans', Cell, vol. 162, no. 5, pp. 1039-1050. https://doi.org/10.1016/j.cell.2015.08.001

TY - JOUR

T1 - Population Variation and Genetic Control of Modular Chromatin Architecture in Humans

AU - Waszak, Sebastian M.

AU - Delaneau, Olivier

AU - Gschwind, Andreas R.

AU - Kilpinen, Helena

AU - Raghav, Sunil K.

AU - Witwicki, Robert M.

AU - Orioli, Andrea

AU - Wiederkehr, Michael

AU - Panousis, Nikolaos I.

AU - Yurovsky, Alisa

AU - Romano-Palumbo, Luciana

AU - Planchon, Alexandra

AU - Bielser, Deborah

AU - Padioleau, Ismael

AU - Udin, Gilles

AU - Thurnheer, Sarah

AU - Hacker, David

AU - Hernandez, Nouria

AU - Reymond, Alexandre

AU - Deplancke, Bart

AU - Dermitzakis, Emmanouil T.

PY - 2015/8/27

Y1 - 2015/8/27

N2 - Summary 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.

AB - Summary 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.

UR - https://www.scopus.com/pages/publications/84940419146

U2 - 10.1016/j.cell.2015.08.001

DO - 10.1016/j.cell.2015.08.001

M3 - Article

C2 - 26300124

SN - 0092-8674

VL - 162

SP - 1039

EP - 1050

JO - Cell

JF - Cell

IS - 5

ER -

Population Variation and Genetic Control of Modular Chromatin Architecture in Humans

Abstract

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