Chen Poshen B, Hung Jui-Hung, Hickman Taylor L, Coles Andrew H, Carey James F, Weng Zhiping, Chu Feixia, Fazzio Thomas G
Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, United States.
Elife. 2013 Dec 3;2:e01557. doi: 10.7554/eLife.01557.
In embryonic stem cells (ESCs), the Tip60 histone acetyltransferase activates genes required for proliferation and silences genes that promote differentiation. Here we show that the class II histone deacetylase Hdac6 co-purifies with Tip60-p400 complex from ESCs. Hdac6 is necessary for regulation of most Tip60-p400 target genes, particularly those repressed by the complex. Unlike differentiated cells, where Hdac6 is mainly cytoplasmic, Hdac6 is largely nuclear in ESCs, neural stem cells (NSCs), and some cancer cell lines, and interacts with Tip60-p400 in each. Hdac6 localizes to promoters bound by Tip60-p400 in ESCs, binding downstream of transcription start sites. Surprisingly, Hdac6 does not appear to deacetylate histones, but rather is required for Tip60-p400 binding to many of its target genes. Finally, we find that, like canonical subunits of Tip60-p400, Hdac6 is necessary for robust ESC differentiation. These data suggest that Hdac6 plays a major role in the modulation of Tip60-p400 function in stem cells. DOI: http://dx.doi.org/10.7554/eLife.01557.001.
在胚胎干细胞（ESC）中，Tip60组蛋白乙酰转移酶激活增殖所需的基因，并使促进分化的基因沉默。我们在此表明，II类组蛋白去乙酰化酶Hdac6与ESC中的Tip60 - p400复合物共同纯化。Hdac6对于大多数Tip60 - p400靶基因的调控是必需的，尤其是那些被该复合物抑制的基因。与分化细胞不同，在分化细胞中Hdac6主要位于细胞质，而在ESC、神经干细胞（NSC）和一些癌细胞系中，Hdac6主要位于细胞核，并在每种细胞中都与Tip60 - p400相互作用。在ESC中，Hdac6定位于与Tip60 - p400结合的启动子上，结合在转录起始位点的下游。令人惊讶的是，Hdac6似乎不会使组蛋白去乙酰化，而是Tip60 - p400与其许多靶基因结合所必需的。最后，我们发现，与Tip60 - p400的典型亚基一样，Hdac6对于ESC的稳健分化是必需的。这些数据表明，Hdac6在干细胞中Tip60 - p400功能的调节中起主要作用。DOI: http://dx.doi.org/10.7554/eLife.01557.001 。
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