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

Coordinated effects of sequence variation on DNA binding, chromatin structure, and transcription.
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序列变化对DNA结合,染色质结构和转录的协调影响。

DOI:
10.1126/science.1242463
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发表时间:
2013-11-08
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Dermitzakis ET
Dermitzakis ET
中科院分区:
其他
文献类型:
--
作者:
Kilpinen H;Waszak SM;Gschwind AR;Raghav SK;Witwicki RM;Orioli A;Migliavacca E;Wiederkehr M;Gutierrez-Arcelus M;Panousis NI;Yurovsky A;Lappalainen T;Romano-Palumbo L;Planchon A;Bielser D;Bryois J;Padioleau I;Udin G;Thurnheer S;Hacker D;Core LJ;Lis JT;Hernandez N;Reymond A;Deplancke B;Dermitzakis ET

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DNA序列变异与基因表达等分子表型的定量变化有关,但其对染色质状态的影响尚不清楚。为了了解染色质和基因调控的遗传控制之间的相互作用,我们量化了人类内转录因子结合、组蛋白修饰和基因表达的等位基因变异。我们发现丰富的等位基因特异性染色质和广泛的本地,短期和长期的等位基因协调之间的研究分子表型。我们观察到遗传对大多数这些表型的影响,组蛋白修饰表现出强烈的上下文依赖性行为。我们的研究结果表明,转录因子作为序列特异性调控基因表达程序的主要介质,组蛋白修饰经常反映主要的调控事件。
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-, 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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