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Coordinated effects of sequence variation on DNA binding, chromatin structure, and transcription. 2013
Helena Kilpinen, and
Sebastian M Waszak, and
Andreas R Gschwind, and
Sunil K Raghav, and
Robert M Witwicki, and
Andrea Orioli, and
Eugenia Migliavacca, and
Michaël Wiederkehr, and
Maria Gutierrez-Arcelus, and
Nikolaos I Panousis, and
Alisa Yurovsky, and
Tuuli Lappalainen, and
Luciana Romano-Palumbo, and
Alexandra Planchon, and
Deborah Bielser, and
Julien Bryois, and
Ismael Padioleau, and
Gilles Udin, and
Sarah Thurnheer, and
David Hacker, and
Leighton J Core, and
John T Lis, and
Nouria Hernandez, and
Alexandre Reymond, and
Bart Deplancke, and
Emmanouil T Dermitzakis
Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland.
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.
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