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Title

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

Authors
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
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PMID: 24136355
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Article (Published version) (526 Kb) - document accessible for UNIGE members only Limited access to UNIGE
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Research group Population Genomics and Genetics of Complex Traits (892)
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(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. https://archive-ouverte.unige.ch/unige:90278

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Deposited on : 2016-12-13

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