The CHR site: definition and genome-wide identification of a cell cycle transcriptional element.

The CHR site: definition and genome-wide identification of a cell cycle transcriptional element.
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DOI:
10.1093/nar/gku696
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发表时间:
2014
影响因子:
14.9
通讯作者:
Engeland K
Engeland K
中科院分区:
生物学2区
文献类型:
--
作者:
Müller GA;Wintsche A;Stangner K;Prohaska SJ;Stadler PF;Engeland K

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细胞周期基因同源区(cell cycle genes homology region,cDNA)是细胞周期晚期基因转录调控的重要元件。已经表明,这些基因由DREAM、MMB和FOXM 1-MuvB控制,并且这些蛋白质复合物可以通过DNA结合位点与DNA接触。然而,它还没有被阐明的典型的CHR的序列变异是功能性的,以及如何频繁的CHR为基础的调节是利用在哺乳动物基因组。在这里,我们定义的频谱功能的可调元件。作为计算荟萃分析的基础,我们确定了新的cDNA序列,并编制了系统发育基序保守以及全基因组蛋白质-DNA结合和基因表达数据。我们在大多数结合DREAM、MMB或FOXM 1-MuvB的细胞周期晚期基因中鉴定了CHR元件。相比之下,Myb和forkhead结合位点在细胞周期早期和晚期基因中的表达不足。我们的研究结果支持一个一般机制:DREAM,MMB和FOXM 1-MuvB复合物与细胞周期晚期基因的顺序结合需要转录因子。两者合计,我们定义了一组CHR调节基因在哺乳动物基因组中,并提供证据表明,DREAM,MMB和FOXM 1-MuvB的细胞周期晚期基因的转录调控中的核心启动子元件。
The cell cycle genes homology region (CHR) has been identified as a DNA element with an important role in transcriptional regulation of late cell cycle genes. It has been shown that such genes are controlled by DREAM, MMB and FOXM1-MuvB and that these protein complexes can contact DNA via CHR sites. However, it has not been elucidated which sequence variations of the canonical CHR are functional and how frequent CHR-based regulation is utilized in mammalian genomes. Here, we define the spectrum of functional CHR elements. As the basis for a computational meta-analysis, we identify new CHR sequences and compile phylogenetic motif conservation as well as genome-wide protein-DNA binding and gene expression data. We identify CHR elements in most late cell cycle genes binding DREAM, MMB, or FOXM1-MuvB. In contrast, Myb- and forkhead-binding sites are underrepresented in both early and late cell cycle genes. Our findings support a general mechanism: sequential binding of DREAM, MMB and FOXM1-MuvB complexes to late cell cycle genes requires CHR elements. Taken together, we define the group of CHR-regulated genes in mammalian genomes and provide evidence that the CHR is the central promoter element in transcriptional regulation of late cell cycle genes by DREAM, MMB and FOXM1-MuvB.
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