KAT-Independent Gene Regulation by Tip60 Promotes ESC Self-Renewal but Not Pluripotency
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Authors
Acharya, DiwashHainer, Sarah J.
Yoon, Yeonsoo
Wang, Feng
Bach, Ingolf
Rivera-Perez, Jaime A.
Fazzio, Thomas G.
UMass Chan Affiliations
Rivera LabDepartment of Pediatrics, Division of Genes and Development
Department of Molecular, Cell, and Cancer Biology
Document Type
Journal ArticlePublication Date
2017-04-25Keywords
Ep400Kat5
Tip60
acetyltransferase
chromatin
development
differentiation
embryonic stem cells
self-renewal
Biochemistry
Cell Biology
Developmental Biology
Enzymes and Coenzymes
Molecular Biology
Pediatrics
Metadata
Show full item recordAbstract
Although histone-modifying enzymes are generally assumed to function in a manner dependent on their enzymatic activities, this assumption remains untested for many factors. Here, we show that the Tip60 (Kat5) lysine acetyltransferase (KAT), which is essential for embryonic stem cell (ESC) self-renewal and pre-implantation development, performs these functions independently of its KAT activity. Unlike ESCs depleted of Tip60, KAT-deficient ESCs exhibited minimal alterations in gene expression, chromatin accessibility at Tip60 binding sites, and self-renewal, thus demonstrating a critical KAT-independent role of Tip60 in ESC maintenance. In contrast, KAT-deficient ESCs exhibited impaired differentiation into mesoderm and endoderm, demonstrating a KAT-dependent function in differentiation. Consistent with this phenotype, KAT-deficient mouse embryos exhibited post-implantation developmental defects. These findings establish separable KAT-dependent and KAT-independent functions of Tip60 in ESCs and during differentiation, revealing a complex repertoire of regulatory functions for this essential chromatin remodeling complex.Source
Cell Rep. 2017 Apr 25;19(4):671-679. doi: 10.1016/j.celrep.2017.04.001. Link to article on publisher's site
DOI
10.1016/j.celrep.2017.04.001Permanent Link to this Item
http://hdl.handle.net/20.500.14038/43552PubMed ID
28445719Related Resources
Rights
Copyright © 2017 The Author(s).Distribution License
http://creativecommons.org/licenses/by-nc-nd/4.0/ae974a485f413a2113503eed53cd6c53
10.1016/j.celrep.2017.04.001