ACTL6a enforces the epidermal progenitor state by suppressing SWI/SNF-dependent induction of KLF4

Xiaomin Bao, Jiong Tang, Vanessa Lopez-Pajares, Shiying Tao, Kun Qu, Gerald R. Crabtree, Paul A. Khavari*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)193-203
Number of pages11
JournalCell stem cell
Volume12
Issue number2
DOIs
StatePublished - Feb 7 2013

Funding

We thank H. Chang and A. Oro for their presubmission review, B. Zarnegar for the FPLC fractions of undifferentiated human keratinocytes, D. Johnston for technical support, and L. Boxer for suggestions and reagents. We thank L. Morcom and P. Bernstein for their administrative assistance. This work is supported by the U.S. Department of Veterans Affairs Office of Research and Development, by NIAMS NIH R01 AR45192 (P.A.K), and by an F32 Award (AR061230) to X. B.

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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