Inhibition of p300 histone acetyltransferase activity in palate mesenchyme cells attenuates Wnt signaling via aberrant E-cadherin expression

Dennis R. Warner, Scott C Smith, Irina A. Smolenkova, M. Michele Pisano, Robert M. Greene

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

p300 is a multifunctional transcriptional coactivator that interacts with numerous transcription factors and exhibits protein/histone acetyltransferase activity. Loss of p300 function in humans and in mice leads to craniofacial defects. In this study, we demonstrated that inhibition of p300 histone acetyltransferase activity with the compound, C646, altered the expression of several genes, including Cdh1 (E-cadherin) in mouse maxillary mesenchyme cells, which are the cells that give rise to the secondary palate. The increased expression of plasma membrane-bound E-cadherin was associated with reduced cytosolic β-catenin, that led to attenuated signaling through the canonical Wnt pathway. Furthermore, C646 reduced both cell proliferation and the migratory ability of these cells. These results suggest that p300 histone acetyltransferase activity is critical for Wnt-dependent palate mesenchymal cell proliferation and migration, both processes that play a significant role in morphogenesis of the palate.

Original languageEnglish (US)
Pages (from-to)32-38
Number of pages7
JournalExperimental Cell Research
Volume342
Issue number1
DOIs
StatePublished - Mar 1 2016
Externally publishedYes

Fingerprint

Histone Acetyltransferases
Palate
Mesoderm
Cadherins
Cell Proliferation
Catenins
Wnt Signaling Pathway
Morphogenesis
Cell Movement
Transcription Factors
Cell Membrane
Gene Expression
p300-CBP-associated factor
Proteins

Keywords

  • C646
  • Craniofacial
  • Embryo
  • Histone acetyltransferase
  • P300
  • Palate
  • Wnt

ASJC Scopus subject areas

  • Cell Biology

Cite this

Inhibition of p300 histone acetyltransferase activity in palate mesenchyme cells attenuates Wnt signaling via aberrant E-cadherin expression. / Warner, Dennis R.; Smith, Scott C; Smolenkova, Irina A.; Pisano, M. Michele; Greene, Robert M.

In: Experimental Cell Research, Vol. 342, No. 1, 01.03.2016, p. 32-38.

Research output: Contribution to journalArticle

Warner, Dennis R. ; Smith, Scott C ; Smolenkova, Irina A. ; Pisano, M. Michele ; Greene, Robert M. / Inhibition of p300 histone acetyltransferase activity in palate mesenchyme cells attenuates Wnt signaling via aberrant E-cadherin expression. In: Experimental Cell Research. 2016 ; Vol. 342, No. 1. pp. 32-38.
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