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首页> 外文期刊>Journal of Cellular Physiology >Selective control of gene expression by CDK9 in human cells.
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Selective control of gene expression by CDK9 in human cells.

机译：选择性控制CDK9基因表达的人类细胞。

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CDK9 associates with T-type cyclins and positively regulates transcriptional elongation by phosphorylating RNA polymerase II (RNAPII) and negative elongation factors. However, it is unclear whether CDK9 is required for transcription of most genes by RNAPII or alternatively plays a role regulating the expression of restricted subsets of genes. We have investigated the direct effects of inhibiting cellular CDK9 activity in global gene expression in human cells by using a dominant-negative form of CDK9 (dnCDK9). We have also compared direct inhibition of cellular CDK9 activity to pharmacological inhibition with flavopiridol (FVP), a CDK inhibitor that potently inhibits CDK9 and cellular transcription. Because of its presumed selectivity for CDK9, FVP has been previously used as a tool to infer the role of CDK9 on global gene expression. DNA microarray analyses described here show that inhibition of gene expression by FVP is consistent with global inhibition of transcription. However, specific inhibition of CDK9 activity with dnCDK9 leads to a distinctive pattern of changes in gene expression, with more genes being specifically upregulated (122) than downregulated (84). Indeed, the expression of many short-lived transcripts downregulated by FVP is not modulated by dnCDK9. Nevertheless, consistently with FVP inhibiting CDK9 activity, a significant number of the genes downregulated/upregulated by dnCDK9 are modulated with a similar trend by FVP. Our data suggests that the potent effects of FVP on transcription are likely to involve inhibition of CTD kinases in addition to CDK9. Our data also suggest complex and gene-specific modulation of gene expression by CDK9.
机译：与细胞周期蛋白和积极衣架CDK9 associates调节转录延伸的磷酸化的RNA聚合酶II (RNAPII)和消极的伸长的因素。不清楚CDK9所需大多数基因的转录RNAPII或或者调节中扮演重要角色的表达限制的基因子集。调查的直接影响吗抑制细胞CDK9全球基因的活动通过使用一个在人类细胞中表达显性负CDK9形式(dnCDK9)。相比直接抑制细胞CDK9药物抑制活动flavopiridol (FVP),一个强有力地CDK抑制剂抑制CDK9和细胞转录。CDK9假定的选择性,FVP被用作一个工具来推断这个角色CDK9全球基因的表达。这里描述的分析表明,抑制基因表达的FVP与全球一致抑制转录。抑制与dnCDK9导致CDK9活动一种独特的基因的变化模式被明确表达,更多的基因调节比表达下调(122)(84)。事实上,许多“短命的”的表达由FVP不是调制记录表达下调dnCDK9。抑制CDK9活动,相当数量的表达下调的基因/ dnCDK9调节的FVP调制与类似的趋势。表明FVP的强有力的影响转录可能涉及抑制CTD激酶除了CDK9。建议的复杂和gene-specific调制CDK9基因表达。

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