Mof-associated complexes have overlapping and unique roles in regulating pluripotency in embryonic stem cells and during differentiation

Elife. 2014 Jun 4;3:e02104. doi: 10.7554/eLife.02104.


The histone acetyltransferase (HAT) Mof is essential for mouse embryonic stem cell (mESC) pluripotency and early development. Mof is the enzymatic subunit of two different HAT complexes, MSL and NSL. The individual contribution of MSL and NSL to transcription regulation in mESCs is not well understood. Our genome-wide analysis show that i) MSL and NSL bind to specific and common sets of expressed genes, ii) NSL binds exclusively at promoters, iii) while MSL binds in gene bodies. Nsl1 regulates proliferation and cellular homeostasis of mESCs. MSL is the main HAT acetylating H4K16 in mESCs, is enriched at many mESC-specific and bivalent genes. MSL is important to keep a subset of bivalent genes silent in mESCs, while developmental genes require MSL for expression during differentiation. Thus, NSL and MSL HAT complexes differentially regulate specific sets of expressed genes in mESCs and during differentiation.

Keywords: ChIP-seq; H4K16ac; Mof (KAT8); bivalent domain; chromosomes; developmental biology; genes; histone acetyltransferase; mouse; pluripotency; stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Cell Cycle
  • Cell Differentiation
  • Cell Nucleus / metabolism
  • Cell Proliferation
  • Chromatography, Gel
  • DNA-Binding Proteins / metabolism*
  • Embryonic Stem Cells / cytology*
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Histone Acetyltransferases / metabolism*
  • Homeostasis
  • Male
  • Mice
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • Protein Binding
  • Transcription, Genetic


  • DNA-Binding Proteins
  • Nsl1 protein, mouse
  • Histone Acetyltransferases
  • Kat8 protein, mouse

Associated data

  • GENBANK/GSE53797
  • GENBANK/GSE56646

Grant support

The funder had no role in study design, data collection and interpretation, or the decision to submit the work for publication.