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

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

Author information

1
Cellular signaling and nuclear dynamics program, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR 7104 - Inserm U 964, Université de Strasbourg, Illkirch, France.
2
Microarrays and deep sequencing platform, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR 7104 - Inserm U 964, Université de Strasbourg, Illkirch, France.
3
Proteomics platform, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR 7104 - Inserm U 964, Université de Strasbourg, Illkirch, France.

Abstract

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

PMID:
24898753
PMCID:
PMC4059888
DOI:
10.7554/eLife.02104
[Indexed for MEDLINE]
Free PMC Article
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