Dataset Information


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

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.


PROVIDER: S-EPMC3661004 | BioStudies | 2013-01-01

REPOSITORIES: biostudies

Similar Datasets

2012-11-30 | E-GEOD-36222 | BioStudies
2012-11-30 | E-GEOD-36222 | ArrayExpress
1969-12-31 | S-SCDT-EMBOR-2018-46734V1 | BioStudies
2017-01-01 | S-EPMC5225026 | BioStudies
2019-01-01 | S-EPMC6736241 | BioStudies
1000-01-01 | S-EPMC4182762 | BioStudies
2009-01-01 | S-EPMC2921580 | BioStudies
2016-11-18 | GSE88859 | GEO
2016-11-18 | GSE88831 | GEO
2007-01-01 | S-EPMC2674110 | BioStudies