Genome-wide evidence for an essential role of the human Staf/ZNF143 transcription factor in bidirectional transcription.
Genome-wide evidence for an essential role of the human Staf/ZNF143 transcription factor in bidirectional transcription.
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DOI：
10.1093/nar/gkq1301
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发表时间：
2011-04
影响因子：
14.9
通讯作者：
Carbon P
中科院分区：
文献类型：
--
作者：
Anno YN;Myslinski E;Ngondo-Mbongo RP;Krol A;Poch O;Lecompte O;Carbon P
在人类基因组中，大约10%的基因是头对头排列的，因此它们的转录起始位点位于相对链上<1 kbp的范围内。在这种构型中，双向启动子通常驱动两个基因的表达。如何从这些特定的启动子进行双向表达构成了一个令人困惑的问题。在这里，通过计算机模拟和生物化学方法的组合，我们证明了hStaf/ZNF 143参与控制不同基因对子集的表达。hStaf/ZNF 143（SBS）的结合位点在双向启动子与单向启动子中过度表达。染色质免疫沉淀分析与一组重要的双向启动子含有推定的SBS显示，93%的人与hStaf/ZNF 143。由双向启动子指导的双报告基因的表达依赖于SBS的完整性，并且需要hStaf/ZNF 143。此外，在某些情况下，功能性SBS位于编码非编码RNA和蛋白质基因的基因对的双向启动子中。值得注意的是，hStaf/ZNF 143本身表现出固有的双向转录活性，并且我们的数据一起提供了hStaf/ZNF 143确实是控制不同蛋白质-蛋白质和蛋白质-非编码RNA基因对表达的转录因子的证明。
In the human genome, ∼10% of the genes are arranged head to head so that their transcription start sites reside within <1 kbp on opposite strands. In this configuration, a bidirectional promoter generally drives expression of the two genes. How bidirectional expression is performed from these particular promoters constitutes a puzzling question. Here, by a combination of in silico and biochemical approaches, we demonstrate that hStaf/ZNF143 is involved in controlling expression from a subset of divergent gene pairs. The binding sites for hStaf/ZNF143 (SBS) are overrepresented in bidirectional versus unidirectional promoters. Chromatin immunoprecipitation assays with a significant set of bidirectional promoters containing putative SBS revealed that 93% of them are associated with hStaf/ZNF143. Expression of dual reporter genes directed by bidirectional promoters are dependent on the SBS integrity and requires hStaf/ZNF143. Furthermore, in some cases, functional SBS are located in bidirectional promoters of gene pairs encoding a noncoding RNA and a protein gene. Remarkably, hStaf/ZNF143 per se exhibits an inherently bidirectional transcription activity, and together our data provide the demonstration that hStaf/ZNF143 is indeed a transcription factor controlling the expression of divergent protein–protein and protein–non-coding RNA gene pairs.
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影响因子：
4.5
作者：
Collins PJ;Kobayashi Y;Nguyen L;Trinklein ND;Myers RM
通讯作者：
Myers RM
DOI：
10.1126/science.1162253
发表时间：
2008-12-19
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Seila AC;Calabrese JM;Levine SS;Yeo GW;Rahl PB;Flynn RA;Young RA;Sharp PA
通讯作者：
Sharp PA
影响因子：
3.5
作者：
Gerard, Marie-Aline;Krol, Alain;Carbon, Philippe
通讯作者：
Carbon, Philippe
影响因子：
7
作者：
Lin, Jane M.;Collins, Patrick J.;Weng, Zhiping
通讯作者：
Weng, Zhiping
影响因子：
3.5
作者：
Koyanagi, KO;Hagiwara, M;Imanishi, T
通讯作者：
Imanishi, T