Tissue-specific direct targets of Caenorhabditis elegans Rb/E2F dictate distinct somatic and germline programs.

Tissue-specific direct targets of Caenorhabditis elegans Rb/E2F dictate distinct somatic and germline programs.
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DOI:
10.1186/gb-2013-14-1-r5
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发表时间:
2013-01-23
期刊:
影响因子:
12.3
通讯作者:
Reinke V
Reinke V
中科院分区:
生物学1区
文献类型:
--
作者:
Kudron M;Niu W;Lu Z;Wang G;Gerstein M;Snyder M;Reinke V

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肿瘤抑制因子Rb/E2F在发育过程中调节基因表达以控制多种组织的分化,尽管它在体内如何指导组织特异性基因调控尚不清楚。我们确定了秀丽隐杆线虫Rb/ e2f样成分在种系、肠道和整个胞体中的全基因组结合谱,并揭示了高度组织特异性的结合模式和靶基因。秀丽隐杆线虫Rb的同源基因LIN-35的染色质关联在种系中受损,但在体细胞中却很强大,这一特征可能决定了两种细胞类型对基因表达的不同影响。在肠道中,LIN-35和Hp1的同源异染色质蛋白HPL-2在许多缺乏E2F的位点协同结合。最后,选定的直接靶基因有助于lin-35突变体的体细胞向种系转化,包括促进H3K36甲基化的体细胞特异性靶基因mes-4,以及在22G小RNA通路中起作用的种系特异性靶基因csr-1。总之,组织特异性结合谱和效应靶基因的鉴定揭示了Rb/E2F在体内控制不同细胞命运的机制的重要见解。
The tumor suppressor Rb/E2F regulates gene expression to control differentiation in multiple tissues during development, although how it directs tissue-specific gene regulation in vivo is poorly understood. We determined the genome-wide binding profiles for Caenorhabditis elegans Rb/E2F-like components in the germline, in the intestine and broadly throughout the soma, and uncovered highly tissue-specific binding patterns and target genes. Chromatin association by LIN-35, the C. elegans ortholog of Rb, is impaired in the germline but robust in the soma, a characteristic that might govern differential effects on gene expression in the two cell types. In the intestine, LIN-35 and the heterochromatin protein HPL-2, the ortholog of Hp1, coordinately bind at many sites lacking E2F. Finally, selected direct target genes contribute to the soma-to-germline transformation of lin-35 mutants, including mes-4, a soma-specific target that promotes H3K36 methylation, and csr-1, a germline-specific target that functions in a 22G small RNA pathway. In sum, identification of tissue-specific binding profiles and effector target genes reveals important insights into the mechanisms by which Rb/E2F controls distinct cell fates in vivo.
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