Sequence features and chromatin structure around the genomic regions bound by 119 human transcription factors.
Sequence features and chromatin structure around the genomic regions bound by 119 human transcription factors.
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DOI：
10.1101/gr.139105.112
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发表时间：
2012-09
期刊：
影响因子：
7
通讯作者：
Weng Z
中科院分区：
文献类型：
--
作者：
Wang J;Zhuang J;Iyer S;Lin X;Whitfield TW;Greven MC;Pierce BG;Dong X;Kundaje A;Cheng Y;Rando OJ;Birney E;Myers RM;Noble WS;Snyder M;Weng Z
染色质免疫沉淀结合高通量测序（ChIP-seq）已成为全基因组定位转录因子（TF）结合区域的主导技术。我们对ENCODE Consortium生成的119个人类TF的457个ChIP-seq数据集进行了综合分析。我们在大多数数据集中发现了高度富集的序列基序，揭示了新的基序并验证了已知的基序。基序位点（TF结合位点）在进化上高度保守，并在DNA酶I消化后显示出不同的足迹。我们经常检测到二级图案，除了典型的图案的TF，表明拴系绑定和多个TF之间的cobinding。我们观察到显着的位置和方向偏好之间的许多cobinding TF。在细胞系中特异性表达的基因通常与该细胞系中附近TF结合的更大发生相关。我们观察到细胞系特异性的二级基序介导的组蛋白脱乙酰酶HDAC2和增强子结合蛋白EP300的结合。TF结合位点位于富含GC、核小体缺失和DNA酶I敏感的区域，两侧是定位良好的核小体，并且这些特征中的许多表现出细胞类型特异性。GC丰富可能有利于调节TF结合，因为当未被TF占据时，这些区域在体内被核小体占据。我们在以TF为中心的Web存储库Factorbook（http：//www.example.com）中展示了我们的分析结果，并将随着更多ENCODE数据的生成不断更新该存储库。
Chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) has become the dominant technique for mapping transcription factor (TF) binding regions genome-wide. We performed an integrative analysis centered around 457 ChIP-seq data sets on 119 human TFs generated by the ENCODE Consortium. We identified highly enriched sequence motifs in most data sets, revealing new motifs and validating known ones. The motif sites (TF binding sites) are highly conserved evolutionarily and show distinct footprints upon DNase I digestion. We frequently detected secondary motifs in addition to the canonical motifs of the TFs, indicating tethered binding and cobinding between multiple TFs. We observed significant position and orientation preferences between many cobinding TFs. Genes specifically expressed in a cell line are often associated with a greater occurrence of nearby TF binding in that cell line. We observed cell-line–specific secondary motifs that mediate the binding of the histone deacetylase HDAC2 and the enhancer-binding protein EP300. TF binding sites are located in GC-rich, nucleosome-depleted, and DNase I sensitive regions, flanked by well-positioned nucleosomes, and many of these features show cell type specificity. The GC-richness may be beneficial for regulating TF binding because, when unoccupied by a TF, these regions are occupied by nucleosomes in vivo. We present the results of our analysis in a TF-centric web repository Factorbook (http://factorbook.org) and will continually update this repository as more ENCODE data are generated.
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影响因子：
30.8
作者：
He, Housheng Hansen;Meyer, Clifford A.;Shin, Hyunjin;Bailey, Shannon T.;Wei, Gang;Wang, Qianben;Zhang, Yong;Xu, Kexin;Ni, Min;Lupien, Mathieu;Mieczkowski, Piotr;Lieb, Jason D.;Zhao, Keji;Brown, Myles;Liu, X. Shirley
通讯作者：
Liu, X. Shirley
DOI：
10.1126/science.1162327
发表时间：
2009-06-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Badis G;Berger MF;Philippakis AA;Talukder S;Gehrke AR;Jaeger SA;Chan ET;Metzler G;Vedenko A;Chen X;Kuznetsov H;Wang CF;Coburn D;Newburger DE;Morris Q;Hughes TR;Bulyk ML
通讯作者：
Bulyk ML
影响因子：
12.3
作者：
Li XY;Thomas S;Sabo PJ;Eisen MB;Stamatoyannopoulos JA;Biggin MD
通讯作者：
Biggin MD
影响因子：
30.8
作者：
Carroll, Jason S.;Meyer, Clifford A.;Brown, Myles
通讯作者：
Brown, Myles
影响因子：
30.8
作者：
John S;Sabo PJ;Thurman RE;Sung MH;Biddie SC;Johnson TA;Hager GL;Stamatoyannopoulos JA
通讯作者：
Stamatoyannopoulos JA