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

Xiangzhi Li,1,2,6 Li Li,4,6 Ruchi Pandey,2 Jung S. Byun,5 Kevin Gardner,5 Zhaohui Qin,4 and Yali Dou2,3,*

www.ncbi.nlm.nih.gov/pubmed/22862943

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 plu-
ripotency. 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 func-
tions 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 develop-
mental programs. Mof is also required for Wdr5
recruitment and H3K4 methylation at key regulatory
loci, highlighting the complexity and interconnectiv-
ity of various chromatin regulators in ESCs.