Chromosome-Biased Binding and Gene Regulation by the Caenorhabditis elegans DRM Complex
Chromosome-Biased Binding and Gene Regulation by the Caenorhabditis elegans DRM Complex
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DOI：
10.1371/journal.pgen.1002074
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发表时间：
2011-05-01
期刊：
影响因子：
4.5
通讯作者：
Hagstrom, Kirsten A.
中科院分区：
文献类型：
--
作者：
Tabuchi, Tomoko M.;Deplancke, Bart;Hagstrom, Kirsten A.
DRM是一种保守的转录因子复合物，包括E2 F/DP和pRB家族蛋白，在发育和癌症中起重要作用。在这里，我们描述的DRM绑定和功能的新方面，揭示了通过全基因组分析秀丽隐杆线虫DRM亚基LIN-54。我们发现，LIN-54 DNA结合活性招募DRM启动子丰富的相邻推定的E2 F/DP和LIN-54结合位点，这表明这两个DNA结合部分一起直接DRM的靶基因。染色质免疫沉淀和基因表达谱揭示DRM在调节细胞分裂、发育和生殖相关基因中的保守作用。我们发现LIN-54促进生殖基因在生殖系中的表达，但阻止胚胎索马中生殖系特异性基因的异位激活。引人注目的是，C。线虫DRM在整个基因组中的作用并不一致：DRM募集基序、DRM结合和DRM调节的胚胎基因都在X染色体上表现不足。然而，在lin-54突变体中下调的种系基因在X染色体上过度表达。我们讨论了常染色体结合DRM的丢失如何增强生殖系X染色体沉默的模型。我们认为，常染色体富集的DRM结合出现在C。这是由于生殖系X染色体沉默和生殖系表达的和必需的靶基因向常染色体的进化再分配。因此，性染色体基因调控可能对基因组组织和转录调控网络产生深远的进化影响。
DRM is a conserved transcription factor complex that includes E2F/DP and pRB family proteins and plays important roles in development and cancer. Here we describe new aspects of DRM binding and function revealed through genome-wide analyses of the Caenorhabditis elegans DRM subunit LIN-54. We show that LIN-54 DNA-binding activity recruits DRM to promoters enriched for adjacent putative E2F/DP and LIN-54 binding sites, suggesting that these two DNA-binding moieties together direct DRM to its target genes. Chromatin immunoprecipitation and gene expression profiling reveals conserved roles for DRM in regulating genes involved in cell division, development, and reproduction. We find that LIN-54 promotes expression of reproduction genes in the germline, but prevents ectopic activation of germline-specific genes in embryonic soma. Strikingly, C. elegans DRM does not act uniformly throughout the genome: the DRM recruitment motif, DRM binding, and DRM-regulated embryonic genes are all under-represented on the X chromosome. However, germline genes down-regulated in lin-54 mutants are over-represented on the X chromosome. We discuss models for how loss of autosome-bound DRM may enhance germline X chromosome silencing. We propose that autosome-enriched binding of DRM arose in C. elegans as a consequence of germline X chromosome silencing and the evolutionary redistribution of germline-expressed and essential target genes to autosomes. Sex chromosome gene regulation may thus have profound evolutionary effects on genome organization and transcriptional regulatory networks.