Cell Stem Cell
Volume 11, Issue 2, 3 August 2012, Pages 163-178
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Article
The Histone Acetyltransferase MOF Is a Key Regulator of the Embryonic Stem Cell Core Transcriptional Network

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Summary

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.

Highlights

► The histone acetyltransferase Mof is essential for ESC self-renewal ► Mof directly regulates the Nanog-mediated ESC core transcriptional network ► Overexpression of Nanog partially rescues Mof deletion phenotypes in ESCs ► Mof regulates Wdr5 recruitment and H3K4 methylation at important loci in ESCs

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These authors contributed equally to this work