Transcription factor binding and modified histones in human bidirectional promoters
Transcription factor binding and modified histones in human bidirectional promoters
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DOI：
10.1101/gr.5623407
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发表时间：
2007-06-01
期刊：
影响因子：
7
通讯作者：
Weng, Zhiping
中科院分区：
文献类型：
--
作者：
Lin, Jane M.;Collins, Patrick J.;Weng, Zhiping
双向启动子由于能够调控两个下游基因（趋异基因）而受到广泛关注。它们也非常丰富，指导人类基因组中约11%基因的转录。我们将DNA序列基序的存在、转录因子的结合和修饰的组蛋白分类为在双向启动子中相对于单向启动子的过度表达、共享或不足。我们发现，一小部分基序，包括GABPA，MYC，E2 F1，E2 F4，NRF-1，CCAAT，YY 1和ACTACAnnTCC在双向启动子中过度表达，而大多数（73%）已知的脊椎动物基序则代表不足。我们进行了染色质免疫沉淀（ChIP），然后对GABPA进行定量PCR，在人类基因组的118个区域，并表明它结合双向启动子比单向启动子更频繁，其位置特异性评分矩阵是高度预测的结合。在双向启动子周围的区域中，活跃转录的特征，例如RNA聚合酶II和修饰的组蛋白H3 K4 me 2、H3 K4 me 3和H3 ac的占据率过高，表明在给定细胞中转录的趋异基因的比例高于其他基因的比例。因此，对全基因组微阵列数据的分析表明，68%的不同基因被转录，而所有人类基因的转录率为44%。通过对公开的ENCODE数据的分析和对GABPA的详细研究，我们对双向启动子进行了广泛和深入的调查，从而对它们的基序组成和双向调控模式进行了生物学研究。
Bidirectional promoters have received considerable attention because of their ability to regulate two downstream genes ( divergent genes). They are also highly abundant, directing the transcription of similar to 11% of genes in the human genome. We categorized the presence of DNA sequence motifs, binding of transcription factors, and modified histones as overrepresented, shared, or underrepresented in bidirectional promoters with respect to unidirectional promoters. We found that a small set of motifs, including GABPA, MYC, E2F1, E2F4, NRF-1, CCAAT, YY1, and ACTACAnnTCC are overrepresented in bidirectional promoters, while the majority (73%) of known vertebrate motifs are underrepresented. We performed chromatin-immunoprecipitation (ChIP), followed by quantitative PCR for GABPA, on 118 regions in the human genome and showed that it binds to bidirectional promoters more frequently than unidirectional promoters, and its position-specific scoring matrix is highly predictive of binding. Signatures of active transcription, such as occupancy of RNA polymerase II and the modified histones H3K4me2, H3K4me3, and H3ac, are overrepresented in regions around bidirectional promoters, suggesting that a higher fraction of divergent genes are transcribed in a given cell than the fraction of other genes. Accordingly, analysis of whole-genome microarray data indicates that 68% of divergent genes are transcribed compared with 44% of all human genes. By combining the analysis of publicly available ENCODE data and a detailed study of GABPA, we survey bidirectional promoters with breadth and depth, leading to biological insights concerning their motif composition and bidirectional regulatory mode.