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首页> 外文期刊>Molecular and Cellular Biology >The E2F transcription factor activates a replication-dependent human H2A gene in early S phase of the cell cycle.
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The E2F transcription factor activates a replication-dependent human H2A gene in early S phase of the cell cycle.

机译：E2F转录因子在细胞周期的早期S期激活复制依赖性人类H2A基因。

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Histone gene expression is restricted to the S phase of the cell cycle. Control is mediated by a complex network of sequence-specific DNA-binding factors and protein-protein interactions in response to cell cycle progression. To further investigate the regulatory functions that are associated at the transcriptional level, we analyzed the regulation of a replication-dependent human H2A.1-H2B.2 gene pair. We found that transcription factor E2F binds specifically to an E2F recognition motif in the H2A.1 promoter region. Activation of the H2A.1 promoter by E2F-1 was shown by use of luciferase reporter constructs of the intergenic promoter region. Overexpression of the human retinoblastoma suppressor gene product RB suppressed E2F-1 mediated transcriptional activation, indicating an E2F-dependent regulation of promoter activity during the G1-to-S-phase transition. Furthermore, the activity of the H2A.1 promoter was also downregulated by overexpression of the RB-related p107, a protein that has been detected in S-phase-specific protein complexes of cyclin A, E2F, and cdk2. In synchronized HeLa cells, expression of luciferase activity was induced at the beginning of DNA synthesis and was dependent on the presence of an E2F-binding site in the H2A.1 promoter. Together with the finding that E2F-binding motifs are highly conserved in H2A promoters of other species, our results suggest that E2F plays an important role in the coordinate regulation of S-phase-specific histone gene expression.
机译：组蛋白基因表达仅限于细胞周期的S期。控制是由序列特异性DNA结合因子和响应细胞周期进程的蛋白质相互作用产生的复杂网络介导的。为了进一步研究在转录水平上相关的调控功能，我们分析了复制依赖性人类H2A.1-H2B.2基因对的调控。我们发现，转录因子E2F与H2A.1启动子区域中的E2F识别基序特异性结合。通过使用基因间启动子区域的萤光素酶报告基因构建体显示了H2A.1启动子被E2F-1激活。人类视网膜母细胞瘤抑制基因产物RB的过表达抑制了E2F-1介导的转录激活，表明在G1到S期的过渡过程中E2F依赖的启动子活性调节。此外，H2A.1启动子的活性也因RB相关p107的过表达而下调，该蛋白已在细胞周期蛋白A，E2F和cdk2的S期特异性蛋白复合物中检测到。在同步的HeLa细胞中，荧光素酶活性的表达在DNA合成开始时就被诱导出来，并且取决于H2A.1启动子中E2F结合位点的存在。连同发现E2F结合基序在其他物种的H2A启动子中高度保守的发现，我们的结果表明E2F在S期特异性组蛋白基因表达的协调调节中起着重要作用。

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