MOF-associated complexes ensure stem cell identity and Xist repression.
Elife
; 3: e02024, 2014 May 19.
Article
em En
| MEDLINE
| ID: mdl-24842875
ABSTRACT
Histone acetyl transferases (HATs) play distinct roles in many cellular processes and are frequently misregulated in cancers. Here, we study the regulatory potential of MYST1-(MOF)-containing MSL and NSL complexes in mouse embryonic stem cells (ESCs) and neuronal progenitors. We find that both complexes influence transcription by targeting promoters and TSS-distal enhancers. In contrast to flies, the MSL complex is not exclusively enriched on the X chromosome, yet it is crucial for mammalian X chromosome regulation as it specifically regulates Tsix, the major repressor of Xist lncRNA. MSL depletion leads to decreased Tsix expression, reduced REX1 recruitment, and consequently, enhanced accumulation of Xist and variable numbers of inactivated X chromosomes during early differentiation. The NSL complex provides additional, Tsix-independent repression of Xist by maintaining pluripotency. MSL and NSL complexes therefore act synergistically by using distinct pathways to ensure a fail-safe mechanism for the repression of X inactivation in ESCs.DOI http//dx.doi.org/10.7554/eLife.02024.001.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Histona Acetiltransferases
/
Células-Tronco Embrionárias
/
RNA Longo não Codificante
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Elife
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Alemanha