Hdac1 and Hdac2 Act Redundantly to Control p63 and p53 Functions in Epidermal Progenitor Cells

Matthew LeBoeuf, Anne Terrell, Sohum Trivedi, Satrajit Sinha, Jonathan A. Epstein, Eric N. Olson, Edward E. Morrisey, Sarah E. Millar

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

Epidermal and hair follicle development from surface ectodermal progenitor cells requires coordinated changes in gene expression. Histone deacetylases alter gene expression programs through modification of chromatin and transcription factors. We find that deletion of ectodermal Hdac1 and Hdac2 results in dramatic failure of hair follicle specification and epidermal proliferation and stratification, phenocopying loss of the key ectodermal transcription factor p63. Although expression of p63 and its positively regulated basal cell targets is maintained in Hdac1/2-deficient ectoderm, targets of p63-mediated repression, including p21, 14-3-3σ, and p16/INK4a, are ectopically expressed, and HDACs bind and are active at their promoter regions in normal undifferentiated keratinocytes. Mutant embryos display increased levels of acetylated p53, which opposes p63 functions, and p53 is required for HDAC inhibitor-mediated p21 expression in keratinocytes. Our data identify critical requirements for HDAC1/2 in epidermal development and indicate that HDAC1/2 directly mediate repressive functions of p63 and suppress p53 activity.

Original languageEnglish (US)
Pages (from-to)807-818
Number of pages12
JournalDevelopmental Cell
Volume19
Issue number6
DOIs
StatePublished - Dec 14 2010

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Hair Follicle
Keratinocytes
Gene expression
Transcription Factors
Stem Cells
Gene Expression
Ectoderm
Histone Deacetylase Inhibitors
Histone Deacetylases
Genetic Promoter Regions
Chromatin
Embryonic Structures
Cells
Specifications

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Hdac1 and Hdac2 Act Redundantly to Control p63 and p53 Functions in Epidermal Progenitor Cells. / LeBoeuf, Matthew; Terrell, Anne; Trivedi, Sohum; Sinha, Satrajit; Epstein, Jonathan A.; Olson, Eric N.; Morrisey, Edward E.; Millar, Sarah E.

In: Developmental Cell, Vol. 19, No. 6, 14.12.2010, p. 807-818.

Research output: Contribution to journalArticle

LeBoeuf, M, Terrell, A, Trivedi, S, Sinha, S, Epstein, JA, Olson, EN, Morrisey, EE & Millar, SE 2010, 'Hdac1 and Hdac2 Act Redundantly to Control p63 and p53 Functions in Epidermal Progenitor Cells', Developmental Cell, vol. 19, no. 6, pp. 807-818. https://doi.org/10.1016/j.devcel.2010.10.015
LeBoeuf, Matthew ; Terrell, Anne ; Trivedi, Sohum ; Sinha, Satrajit ; Epstein, Jonathan A. ; Olson, Eric N. ; Morrisey, Edward E. ; Millar, Sarah E. / Hdac1 and Hdac2 Act Redundantly to Control p63 and p53 Functions in Epidermal Progenitor Cells. In: Developmental Cell. 2010 ; Vol. 19, No. 6. pp. 807-818.
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