Coordinated Effects of Sequence Variation on DNA Binding, Chromatin Structure, and Transcription

作者：Kilpinen Helena; Waszak Sebastian M; Gschwind Andreas R; Raghav Sunil K; Witwicki Robert M; Orioli Andrea; Migliavacca Eugenia; Wiederkehr Michael; Gutierrez Arcelus Maria; Panousis Nikolaos I; Yurovsky Alisa; Lappalainen Tuuli; Romano Palumbo Luciana; Planchon Alexandra; Bielser Deborah; Bryois Julien; Padioleau Ismael; Udin Gilles; Thurnheer Sarah; Hacker David; Core Leighton J; Lis John T; Hernandez Nouria^*; Reymond Alexandre; Deplancke Bart

来源：Science, 2013, 342(6159): 744-747.

DOI：10.1126/science.1242463

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.

• 出版日期2013-11-8