Discovery of active enhancers through bidirectional expression of short transcripts.
Discovery of active enhancers through bidirectional expression of short transcripts.
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DOI：
10.1186/gb-2011-12-11-r113
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发表时间：
2011-11-14
期刊：
影响因子：
12.3
通讯作者：
Sethupathy P
中科院分区：
文献类型：
--
作者：
Melgar MF;Collins FS;Sethupathy P
远程调控元件，如增强子，对组织特异性基因表达模式施加实质性控制。在不同细胞类型中全基因组功能增强子的发现对于我们理解基因组功能和人类疾病病因学是重要的。在这项研究中，我们开发了一种计算机方法来模拟先前报道的转录暂停现象，伴随着转录分化，在活性启动子处。然后，我们使用该模型大规模预测非启动子相关的短转录本双向表达。我们对dna酶超敏位点、组蛋白H3赖氨酸27乙酰化（H3K27ac）和其他与活性增强子相关的染色质标记的预测显著增强，而不是静止或抑制增强子。我们还检测到ccctc因子（CTCF）全基因组结合位点的适度双向表达，特别是那些与H3K27ac重叠的位点。我们的研究结果表明，从启动子-近端转录暂停中了解到的短转录本的双向表达特征可以用于预测全基因组范围内活跃的远程调控元件，部分可能是由于RNA聚合酶与增强子区域的特定关联。
Long-range regulatory elements, such as enhancers, exert substantial control over tissue-specific gene expression patterns. Genome-wide discovery of functional enhancers in different cell types is important for our understanding of genome function as well as human disease etiology. In this study, we developed an in silico approach to model the previously reported phenomenon of transcriptional pausing, accompanied by divergent transcription, at active promoters. We then used this model for large-scale prediction of non-promoter-associated bidirectional expression of short transcripts. Our predictions were significantly enriched for DNase hypersensitive sites, histone H3 lysine 27 acetylation (H3K27ac), and other chromatin marks associated with active rather than poised or repressed enhancers. We also detected modest bidirectional expression at binding sites of the CCCTC-factor (CTCF) genome-wide, particularly those that overlap H3K27ac. Our findings indicate that the signature of bidirectional expression of short transcripts, learned from promoter-proximal transcriptional pausing, can be used to predict active long-range regulatory elements genome-wide, likely due in part to specific association of RNA polymerase with enhancer regions.
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影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
DOI：
10.1126/science.1181421
发表时间：
2010-01-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Nechaev S;Fargo DC;dos Santos G;Liu L;Gao Y;Adelman K
通讯作者：
Adelman K
影响因子：
64.5
作者：
Levine M
通讯作者：
Levine M
影响因子：
64.5
作者：
Kim, Tae Hoon;Abdullaev, Ziedulla K.;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
4
作者：
Li J;Gilmour DS
通讯作者：
Gilmour DS