The Histone Acetyltransferase MOF is a Key Regulator of the Embryonic Stem Cell Core Transcriptional Network

• Type of Material: Article
• Authors: Xiangzhi Li, University of Michigan; Li Li, Emory University; Ruchi Pandey, University of Michigan; Jung S. Byun, NIH; Kevin Gardner, NIH; Zhaohui Qin, Emory University; Yali Dou, University of Michigan
• Language: English
• Date: 2012-08-03
• Publisher: Elsevier (Cell Press): 12 month embargo
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.stem.2012.04.023
• Title of Journal or Parent Work: Cell Stem Cell
• ISSN: 1934-5909
• Volume: 11
• Issue: 2
• Start Page: 163
• End Page: 178
• Grant/Funding Information: This work is supported by NIGMS (R01GM082856) and American Cancer Society (RSG 117573) grants to YD, NHGRI (R01HG005119) grant to ZQ and NSFC (31171428) grant to XL.
• Keywords: PLURIPOTENCY; ES CELLS; DROSOPHILA; NANOG; SELF-RENEWAL; Cell Biology; Science & Technology; Life Sciences & Biomedicine; DIFFERENTIATION; CHROMATIN-STRUCTURE; METHYLATION; Cell & Tissue Engineering; H4-K16 ACETYLATION; DOSAGE COMPENSATION
• Research Categories: Biology, Biostatistics; Biology, Bioinformatics; Health Sciences, Public Health

Abstract

Pluripotent embryonic stem cells (ESCs) maintain self-renewal and the potential for rapid response to differentiation cues. Both ESC features are subject to epigenetic regulation. Here we show that the histone acetyltransferase Mof plays an essential role in the maintenance of ESC self-renewal and pluripotency. ESCs with Mof deletion lose characteristic morphology, alkaline phosphatase (AP) staining, and differentiation potential. They also have aberrant expression of the core transcription factors Nanog, Oct4, and Sox2. Importantly, the phenotypes of Mof null ESCs can be partially suppressed by Nanog overexpression, supporting the idea that Mof functions as an upstream regulator of Nanog in ESCs. Genome-wide ChIP-sequencing and transcriptome analyses further demonstrate that Mof is an integral component of the ESC core transcriptional network and that Mof primes genes for diverse developmental programs. Mof is also required for Wdr5 recruitment and H3K4 methylation at key regulatory loci, highlighting the complexity and interconnectivity of various chromatin regulators in ESCs. © 2012 Elsevier Inc.