Agroup led by Zhang Wensheng at Cam-Su Genomic Resource Center, SoochowUniversity Medical school and a team led by Kathrin Plath at the University ofCalifornia, Los Angeles, USA have published theircollaborative works on the 3rd January, 2019 in Cell Stem Cell.Their works uncover unique mechanism by which a specific BAF subunit and PRC2subunits regulate genes important for the ESC differentiation.
BAFcomplexes are composed of different subunits with varying functional anddevelopmental roles, although many subunits have not been examined in depth.Here we show that the Baf45 subunit Dpf2 maintains pluripotency and ESCdifferentiation potential. Dpf2 co-occupies enhancers with Oct4, Sox2, p300,and the BAF subunit Brg1, and deleting Dpf2 perturbs ESC self-renewal, inducesrepression of Tbx3, and impairs mesendodermal differentiation withoutdramatically altering Brg1 localization. Mesendodermal differentiation can berescued by restoring Tbx3 expression, whose distal enhancer is positivelyregulated by Dpf2-dependent H3K27ac maintenance and recruitment of pluripotencyTFs and Brg1. In contrast, the PRC2 subunit Eed binds an intragenic Tbx3enhancer to oppose Dpf2-dependent Tbx3 expression and mesendodermaldifferentiation. The PRC2 subunit Ezh2 likewise opposes Dpf2-dependentdifferentiation through a distinct mechanism involving Nanog repression.Together, these findings delineate distinct mechanistic roles for specific BAFand PRC2 subunits during ESC differentiation.
W Zhang et al. (2019) TheBAF and PRC2 Complex Subunits Dpf2 and Eed Antagonistically Converge on Tbx3 toControl ESC Differentiation. Cell Stem Cell. DOI:https://doi.org/10.1016/j.stem.2018.12.001