Coordinated effects of sequence variation on DNA binding, chromatin structure, and transcription

Kilpinen, Leena Helena; Waszak, Sebastian M; Gschwind, Andreas R; Raghav, Sunil K; Witwicki, Robert M; Orioli, Andrea; Migliavacca, Eugenia; Wiederkehr, Michaël; Gutierrez Arcelus, Maria; Panousis, Nikolaos; Yurovsky, Alisa; Lappalainen, Tuuli Emilia; Romano, Luciana; Planchon, Alexandra; Penet, Deborah Danièle; Bryois, Julien; Padioleau, Ismael; Udin, Gilles; Thurnheer, Sarah; Hacker, David; Core, Leighton J; Lis, John T; Hernandez, Nouria; Reymond, Alexandre; Deplancke, Bart; Dermitzakis, Emmanouil

doi:10.1126/science.1242463

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Title		Coordinated effects of sequence variation on DNA binding, chromatin structure, and transcription
Authors		Kilpinen, Leena Helena Waszak, Sebastian M Gschwind, Andreas R Raghav, Sunil K Witwicki, Robert M Orioli, Andrea Migliavacca, Eugenia Wiederkehr, Michaël Gutierrez Arcelus, Maria Panousis, Nikolaos Yurovsky, Alisa Lappalainen, Tuuli Emilia Romano, Luciana Planchon, Alexandra Penet, Deborah Danièle Bryois, Julien Padioleau, Ismael Udin, Gilles Thurnheer, Sarah Hacker, David Core, Leighton J Lis, John T Hernandez, Nouria Reymond, Alexandre Deplancke, Bart Dermitzakis, Emmanouil show all authors [1 - 26]
Published in		Science. 2013, vol. 342, no. 6159, p. 744-747
Abstract		DNA sequence variation has been associated with quantitative changes in molecular phenotypes such as gene expression, but its impact on chromatin states is poorly characterized. To understand the interplay between chromatin and genetic control of gene regulation, we quantified allelic variability in transcription factor binding, histone modifications, and gene expression within humans. We found abundant allelic specificity in chromatin and extensive local, short-range, and long-range allelic coordination among the studied molecular phenotypes. We observed genetic influence on most of these phenotypes, with histone modifications exhibiting strong context-dependent behavior. Our results implicate transcription factors as primary mediators of sequence-specific regulation of gene expression programs, with histone modifications frequently reflecting the primary regulatory event.
Keywords		Alleles — Base Sequence/genetics — Binding Sites/genetics — Chromatin/chemistry/metabolism — DNA/chemistry/metabolism — Gene Expression Regulation — Genetic Variation — Histones/chemistry/metabolism — Humans — Polymorphism, Single Nucleotide — Promoter Regions, Genetic — Transcription Factors/metabolism — Transcription, Genetic
Identifiers		DOI: 10.1126/science.1242463 PMID: 24136355
Full text		Article (Published version) (526 Kb) - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement
Research group		Population Genomics and Genetics of Complex Traits (892)
Citation (ISO format)		KILPINEN, Leena Helena et al. Coordinated effects of sequence variation on DNA binding, chromatin structure, and transcription. In: Science, 2013, vol. 342, n° 6159, p. 744-747. doi: 10.1126/science.1242463 https://archive-ouverte.unige.ch/unige:90278