1. The BAF and PRC2 Complex Subunits Dpf2 and Eed Antagonistically Converge on Tbx3 to Control ESC Differentiation.
- Author
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Zhang, Wensheng, Chronis, Constantinos, Chen, Xi, Zhang, Heyao, Spalinskas, Rapolas, Pardo, Mercedes, Chen, Liangliang, Wu, Guangming, Zhu, Zhexin, Yu, Yong, Yu, Lu, Choudhary, Jyoti, Nichols, Jennifer, Parast, Mana M, Greber, Boris, Sahlén, Pelin, and Plath, Kathrin
- Subjects
Animals ,Mice ,Knockout ,Mice ,DNA-Binding Proteins ,T-Box Domain Proteins ,Histones ,Protein Subunits ,Transcription Factors ,Cell Cycle ,Apoptosis ,Cell Differentiation ,Embryonic Stem Cells ,Polycomb Repressive Complex 2 ,Nanog Homeobox Protein ,BAF complex ,PRC2 complex ,cell fate decision ,differentiation ,embryonic stem cells ,enhancers ,histone modification ,pluripotency ,self-renewal ,Stem Cell Research - Embryonic - Non-Human ,Stem Cell Research ,Developmental Biology ,Biological Sciences ,Medical and Health Sciences - Abstract
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.
- Published
- 2019