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

Waszak, Sebastian M
Gschwind, Andreas R
Raghav, Sunil K
Witwicki, Robert M
Orioli, Andrea
Migliavacca, Eugenia
Wiederkehr, Michaël
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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 AllelesBase Sequence/geneticsBinding Sites/geneticsChromatin/chemistry/metabolismDNA/chemistry/metabolismGene Expression RegulationGenetic VariationHistones/chemistry/metabolismHumansPolymorphism, Single NucleotidePromoter Regions, GeneticTranscription Factors/metabolismTranscription, Genetic
PMID: 24136355
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Research group Population Genomics and Genetics of Complex Traits (892)
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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

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Deposited on : 2016-12-13

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