The histone H2B-specific ubiquitin ligase RNF20/hBRE1 acts as a putative tumor suppressor through selective regulation of gene expression
The histone H2B-specific ubiquitin ligase RNF20/hBRE1 acts as a putative tumor suppressor through selective regulation of gene expression
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DOI：
10.1101/gad.1703008
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发表时间：
2008-10-01
影响因子：
10.5
通讯作者：
Oren, Moshe
中科院分区：
文献类型：
--
作者：
Shema, Efrat;Tirosh, Itay;Oren, Moshe
组蛋白的单泛素化参与了关键的调控过程。我们通过减少hBRE1/RNF20的表达来探索组蛋白H2B泛素化在人类细胞中的作用。hBRE1/RNF20是主要的H2B特异性E3泛素连接酶。虽然H_2B泛素化与转录基因广泛相关，但只有一部分基因在转录上受到RNF20缺失和H_2B泛素化缺失的影响。依赖于RNF20的基因表达包括组蛋白H_2A和H_2B以及肿瘤抑制基因P53。相反，RNF20抑制了几个原癌基因的表达，这些基因优先驻留在封闭的染色质中，并适度转录，尽管带有通常与高转录速率相关的标记。值得注意的是，RNF20缺失增强了表皮生长因子(EGF)的转录效应，增加了细胞迁移，并引发了转化和肿瘤发生。此外，在肿瘤中还观察到频繁的RNF20启动子高甲基化。因此，RNF20可能是一种假定的肿瘤抑制因子，通过选择性调节一组不同的基因发挥作用。
Histone monoubiquitylation is implicated in critical regulatory processes. We explored the roles of histone H2B ubiquitylation in human cells by reducing the expression of hBRE1/RNF20, the major H2B-specific E3 ubiquitin ligase. While H2B ubiquitylation is broadly associated with transcribed genes, only a subset of genes was transcriptionally affected by RNF20 depletion and abrogation of H2B ubiquitylation. Gene expression dependent on RNF20 includes histones H2A and H2B and the p53 tumor suppressor. In contrast, RNF20 suppresses the expression of several proto-oncogenes, which reside preferentially in closed chromatin and are modestly transcribed despite bearing marks usually associated with high transcription rates. Remarkably, RNF20 depletion augmented the transcriptional effects of epidermal growth factor (EGF), increased cell migration, and elicited transformation and tumorigenesis. Furthermore, frequent RNF20 promoter hypermethylation was observed in tumors. RNF20 may thus be a putative tumor suppressor, acting through selective regulation of a distinct subset of genes.