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

doi:10.1016/j.stem.2012.12.014

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

Molecular Biosciences

Research output: Contribution to journal › Article › peer-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 language	English (US)
Pages (from-to)	193-203
Number of pages	11
Journal	Cell stem cell
Volume	12
Issue number	2
DOIs	https://doi.org/10.1016/j.stem.2012.12.014
State	Published - 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

Access to Document

10.1016/j.stem.2012.12.014

Cite this

@article{1e42be022c2f45008276e87bdcac1a7a,

title = "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.",

author = "Xiaomin Bao and Jiong Tang and Vanessa Lopez-Pajares and Shiying Tao and Kun Qu and Crabtree, {Gerald R.} and Khavari, {Paul A.}",

note = "Funding Information: 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. ",

year = "2013",

month = feb,

day = "7",

doi = "10.1016/j.stem.2012.12.014",

language = "English (US)",

volume = "12",

pages = "193--203",

journal = "Cell stem cell",

issn = "1934-5909",

publisher = "Cell Press",

number = "2",

}

TY - JOUR

T1 - ACTL6a enforces the epidermal progenitor state by suppressing SWI/SNF-dependent induction of KLF4

AU - Bao, Xiaomin

AU - Tang, Jiong

AU - Lopez-Pajares, Vanessa

AU - Tao, Shiying

AU - Qu, Kun

AU - Crabtree, Gerald R.

AU - Khavari, Paul A.

N1 - Funding Information: 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.

PY - 2013/2/7

Y1 - 2013/2/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84873595705&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84873595705&partnerID=8YFLogxK

U2 - 10.1016/j.stem.2012.12.014

DO - 10.1016/j.stem.2012.12.014

M3 - Article

C2 - 23395444

AN - SCOPUS:84873595705

SN - 1934-5909

VL - 12

SP - 193

EP - 203

JO - Cell stem cell

JF - Cell stem cell

IS - 2

ER -

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

Abstract

Funding

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this