Transcriptional activation of polycomb-repressed genes by ZRF1
Transcriptional activation of polycomb-repressed genes by ZRF1
复制标题
DOI：
10.1038/nature09574
复制
发表时间：
2010-12-23
期刊：
影响因子：
64.8
通讯作者：
Di Croce, Luciano
中科院分区：
文献类型：
--
作者：
Richly, Holger;Rocha-Viegas, Luciana;Di Croce, Luciano
组蛋白的共价修饰是协调染色质动力学和转录的基础(1-3)。这种表观遗传标记的一个例子是组蛋白的单泛素化，主要发生在组蛋白 H2A 和 H2B(4-6) 处。组蛋白 H2A 泛素化与多梳介导的转录沉默有关(7-9)。然而，泛素标记在沉默过程中的确切作用仍然难以捉摸。在这里，我们在人类细胞系中证明，当 ZRF1（zuotin 相关因子 1）通过位于进化上保守的 zuotin 结构域中的新型泛素相互作用结构域在 Lys 119 处被泛素化时，ZRF1（zuotin 相关因子 1）会被特异性招募到组蛋白 H2A。在分化开始时，ZRF1 特异性地取代染色质中的多梳抑制复合物 1 (PRC1)，并促进转录激活。 ZRF1、RING1B 和 H2A-泛素靶标的全基因组图谱揭示了其参与大量多梳靶基因的调节，强调了 ZRF1 在细胞命运决定中的关键作用。我们在这里提供了将多梳抑制基因切换到活跃状态的分子机制模型。
Covalent modification of histones is fundamental in orchestrating chromatin dynamics and transcription(1-3). One example of such an epigenetic mark is the mono-ubiquitination of histones, which mainly occurs at histone H2A and H2B(4-6). Ubiquitination of histone H2A has been implicated in polycomb-mediated transcriptional silencing(7-9). However, the precise role of the ubiquitin mark during silencing is still elusive. Here we show in human cell lines that ZRF1 (zuotin-related factor 1) is specifically recruited to histone H2A when it is ubiquitinated at Lys 119 by means of a novel ubiquitin-interacting domain that is located in the evolutionarily conserved zuotin domain. At the onset of differentiation, ZRF1 specifically displaces polycomb-repressive complex 1 (PRC1) from chromatin and facilitates transcriptional activation. A genome-wide mapping of ZRF1, RING1B and H2A-ubiquitin targets revealed its involvement in the regulation of a large set of polycomb target genes, emphasizing the key role ZRF1 has in cell fate decisions. We provide here a model of the molecular mechanism of switching polycomb-repressed genes to an active state.