TY - JOUR TI - MOF-associated complexes ensure stem cell identity and Xist repression AU - Chelmicki, Tomasz AU - Dündar, Friederike AU - Turley, Matthew James AU - Khanam, Tasneem AU - Aktas, Tugce AU - Ramírez, Fidel AU - Gendrel, Anne-Valerie AU - Wright, Patrick Rudolf AU - Videm, Pavankumar AU - Backofen, Rolf AU - Heard, Edith AU - Manke, Thomas AU - Akhtar, Asifa A2 - Reinberg, Danny VL - 3 PY - 2014 DA - 2014/05/19 SP - e02024 C1 - eLife 2014;3:e02024 DO - 10.7554/eLife.02024 UR - https://doi.org/10.7554/eLife.02024 AB - 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. KW - D. melanogaster KW - epigenetic KW - chromatin KW - transcription KW - acetylation KW - X inactivation JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -