ACTL6a Enforces the Epidermal Progenitor State by Suppressing SWI/SNF-Dependent Induction of KLF4

详细信息    查看全文

• 作者：Xiaomin Bao¹ ; Jiong Tang² ; Vanessa Lopez-Pajares¹ ; Shiying Tao¹ ; Kun Qu¹ ; Gerald R. Crabtree² ; Paul A. Khavari¹ ; ³ ; ^{khavari@stanford.edu}
• 刊名：Cell Stem Cell
• 出版年：2013
• 出版时间：7 February, 2013
• 年：2013
• 卷：12
• 期：2
• 页码：193-203
• 全文大小：1791 K

文摘

| Figures/TablesFigures/Tables | ReferencesReferences

Summary

Somatic progenitors suppress differentiation to maintain tissue self-renewal. The mammalian SWI/SNF chromatin-remodeling complex regulates nucleosome packaging to control differentiation in embryonic and adult stem cells. Catalytic Brg1 and Brm subunits are required for these processes; however, the roles of SWI/SNF regulatory subunits are not fully understood. Here, we show that ACTL6a/BAF53A modulates the SWI/SNF complex to suppress differentiation in epidermis. Conditional loss of ACTL6a resulted in terminal differentiation, cell-cycle exit, and hypoplasia, whereas ectopic expression of ACTL6a promoted the progenitor state. A significant portion of genes regulated by ACTL6a were found to also be targets of KLF4, a known activator of epidermal?differentiation. Mechanistically, we show that ACTL6a prevents SWI/SNF complex binding to promoters of KLF4 and other differentiation genes and that SWI/SNF catalytic subunits are required for full induction of KLF4 targets. Thus, ACTL6a controls the epidermal progenitor state by sequestering SWI/SNF to prevent activation of differentiation programs.