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Scientists from Soochow University Medical School uncover the mechanisms of chromatin remodelling complex on ESC differentiation

A group led by Zhang Wensheng at Cam-Su Genomic Resource Center, Soochow University Medical school and a team led by Kathrin Plath at the University of California, Los Angeles, USA have published their collaborative works on the 3rd January, 2019 in Cell Stem Cell. Their works uncover unique mechanism by which a speci?c BAF subunit and PRC2 subunits regulate genes important for the ESC differentiation.

BAF complexes are composed of different subunits with varying functional and developmental roles, although many subunits have not been examined in depth. Here we show that the Baf45 subunit Dpf2 maintains pluripotency and ESC differentiation potential. Dpf2 co-occupies enhancers with Oct4, Sox2, p300, and the BAF subunit Brg1, and deleting Dpf2 perturbs ESC self-renewal, induces repression of Tbx3, and impairs mesendodermal differentiation without dramatically altering Brg1 localization. Mesendodermal differentiation can be rescued by restoring Tbx3 expression, whose distal enhancer is positively regulated by Dpf2-dependent H3K27ac maintenance and recruitment of pluripotency TFs and Brg1. In contrast, the PRC2 subunit Eed binds an intragenic Tbx3 enhancer to oppose Dpf2-dependent Tbx3 expression and mesendodermal differentiation. The PRC2 subunit Ezh2 likewise opposes Dpf2-dependent differentiation through a distinct mechanism involving Nanog repression. Together, these findings delineate distinct mechanistic roles for specific BAF and PRC2 subunits during ESC differentiation.


W Zhang et al. (2019) The BAF and PRC2 Complex Subunits Dpf2 and Eed Antagonistically Converge on Tbx3 to Control ESC Differentiation. Cell Stem Cell. DOI: https://doi.org/10.1016/j.stem.2018.12.001

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