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

Science 2013 Nov 17;342(6159):744-7. Epub 2013 Oct 17.

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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http://dx.doi.org/10.1126/science.1242463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5502466PMC
November 2013
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