DNA breathing dynamics distinguish binding from nonbinding consensus sites for transcription factor YY1 in cells.
DNA breathing dynamics distinguish binding from nonbinding consensus sites for transcription factor YY1 in cells.
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DOI：
10.1093/nar/gks758
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发表时间：
2012-11-01
影响因子：
14.9
通讯作者：
Usheva A
中科院分区：
文献类型：
--
作者：
Alexandrov BS;Fukuyo Y;Lange M;Horikoshi N;Gelev V;Rasmussen KØ;Bishop AR;Usheva A
主要基因表达调控因子转录因子及其DNA结合位点的全基因组定位对于描述细胞行为和表型多样性具有重要意义。目前，用于预测基因组TF结合的方法产生大量的假阳性，最有可能是由于对蛋白质-DNA结合的生理化学机制的描述不足。越来越多的证据表明，在细胞中，双链DNA（dsDNA）会发生局部短暂的链分离（呼吸），这有助于基因组功能。通过使用位点特异性染色质免疫沉淀，凝胶位移，生物基数据，和我们的模型，准确地描述了双链DNA的熔化行为和呼吸动力学，我们报告了一个特定的DNA呼吸分布在YY 1结合位点的细胞。我们发现，基因组侧翼序列的变化和单核苷酸多态性，可能会产生长期影响的DNA动力学和预定YY 1结合。普遍存在的TF YY 1在基本的生物过程中具有基本的作用，通过激活，启动或抑制转录，这取决于它结合的序列背景。我们预计，共识结合序列连同相关的DNA动力学概况可能会显着提高基因组TF结合位点和TF结合相关的功能SNP的准确性。
The genome-wide mapping of the major gene expression regulators, the transcription factors (TFs) and their DNA binding sites, is of great importance for describing cellular behavior and phenotypic diversity. Presently, the methods for prediction of genomic TF binding produce a large number of false positives, most likely due to insufficient description of the physiochemical mechanisms of protein–DNA binding. Growing evidence suggests that, in the cell, the double-stranded DNA (dsDNA) is subject to local transient strands separations (breathing) that contribute to genomic functions. By using site-specific chromatin immunopecipitations, gel shifts, BIOBASE data, and our model that accurately describes the melting behavior and breathing dynamics of dsDNA we report a specific DNA breathing profile found at YY1 binding sites in cells. We find that the genomic flanking sequence variations and SNPs, may exert long-range effects on DNA dynamics and predetermine YY1 binding. The ubiquitous TF YY1 has a fundamental role in essential biological processes by activating, initiating or repressing transcription depending upon the sequence context it binds. We anticipate that consensus binding sequences together with the related DNA dynamics profile may significantly improve the accuracy of genomic TF binding sites and TF binding-related functional SNPs.
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影响因子：
14.9
作者：
Alexandrov BS;Gelev V;Monisova Y;Alexandrov LB;Bishop AR;Rasmussen KØ;Usheva A
通讯作者：
Usheva A
DOI：
10.1126/science.1183621
发表时间：
2010-04-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kasowski M;Grubert F;Heffelfinger C;Hariharan M;Asabere A;Waszak SM;Habegger L;Rozowsky J;Shi M;Urban AE;Hong MY;Karczewski KJ;Huber W;Weissman SM;Gerstein MB;Korbel JO;Snyder M
通讯作者：
Snyder M
影响因子：
4.5
作者：
Kaplan T;Li XY;Sabo PJ;Thomas S;Stamatoyannopoulos JA;Biggin MD;Eisen MB
通讯作者：
Eisen MB
影响因子：
46.9
作者：
Tompa, M;Li, N;Zhu, Z
通讯作者：
Zhu, Z
影响因子：
4.3
作者：
Alexandrov, Boian S.;Gelev, Vladimir;Usheva, Anny
通讯作者：
Usheva, Anny