UMMS Affiliation

Program in Gene Function and Expression; Program in Bioinformatics and Integrative Biology; Department of Biochemistry and Molecular Pharmacology; Program in Molecular Medicine

Publication Date

12-3-2013

Document Type

Article

Disciplines

Biochemistry | Cellular and Molecular Physiology | Developmental Biology | Molecular Biology

Abstract

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.

Keywords

Hdac6, Kat5, Tip60, chromatin, stem cells

Rights and Permissions

Copyright 2013, Chen et al.

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

DOI of Published Version

10.7554/eLife.01557

Source

Chen PB, Hung JH, Hickman TL, Coles AH, Carey JF, Weng Z, Chu F, Fazzio TG. Hdac6 regulates Tip60-p400 function in stem cells. Elife. 2013 Dec 3;2:e01557. doi: 10.7554/eLife.01557. Link to article on publisher's site

Journal/Book/Conference Title

eLife

Related Resources

Link to Article in PubMed

PubMed ID

24302573

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