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Publication : MOF-associated complexes ensure stem cell identity and Xist repression.

First Author  Chelmicki T Year  2014
Journal  Elife Volume  3
Pages  e02024 PubMed ID  24842875
Mgi Jnum  J:313850 Mgi Id  MGI:6207704
Doi  10.7554/eLife.02024 Citation  Chelmicki T, et al. (2014) MOF-associated complexes ensure stem cell identity and Xist repression. Elife 3:e02024
abstractText  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.
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