A TFTC/STAGA module mediates histone H2A and H2B deubiquitination, coactivates nuclear receptors, and counteracts heterochromatin silencing
A TFTC/STAGA module mediates histone H2A and H2B deubiquitination, coactivates nuclear receptors, and counteracts heterochromatin silencing
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DOI：
10.1016/j.molcel.2007.12.011
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发表时间：
2008-01-18
期刊：
影响因子：
16
通讯作者：
Devys, Didier
中科院分区：
文献类型：
--
作者：
Zhao, Yue;Lang, Guillaume;Devys, Didier
转录激活因子、几种不同的共激活因子和通用转录因子对于进入致密染色质结构中的特定位点是必要的，以允许 RNA 聚合酶 11 (Pol II) 转录的精确起始。组蛋白乙酰转移酶 (HAT) 复合物与启动子周围的染色质松动有关，从而与基因激活有关。在这里，我们证明含有 2 MDa GCN5 HAT 的后生动物 TTC/STAGA 复合物含有组蛋白 H2A 和 H2B 去泛素酶活性。我们已经确定了 TTC/STAGA 的另外三个亚基（ATXN7L3、USP22 和 ENY2），它们形成了去泛素化模块。重要的是，我们发现该模块是果蝇位置效应杂色的增强子。此外，我们证明 ATXN7L3、USP22 和 ENY2 是核受体完整转录活性所需的辅助因子。因此，TFTC/STAGA HAT 复合物的去泛素酶活性对于抵消异染色质沉默是必要的，并作为体内核受体激活的正辅助因子。
Transcriptional activators, several different coactivators, and general transcription factors are necessary to access specific loci in the dense chromatin structure to allow precise initiation of RNA polymerase 11 (Pol II) transcription. Histone acetyltransferase (HAT) complexes were implicated in loosening the chromatin around promoters and thus in gene activation. Here we demonstrate that the 2 MDa GCN5 HAT-containing metazoan TFTC/STAGA complexes contain a histone H2A and H2B deubiquitinase activity. We have identified three additional subunits of TFTC/STAGA (ATXN7L3, USP22, and ENY2) that form the deubiquitination module. Importantly, we found that this module is an enhancer of position effect variegation in Drosophila. Furthermore, we demonstrate that ATXN7L3, USP22, and ENY2 are required as cofactors for the full transcriptional activity by nuclear receptors. Thus, the deubiquitinase activity of the TFTC/STAGA HAT complex is necessary to counteract heterochromatin silencing and acts as a positive cofactor for activation by nuclear receptors in vivo.