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

Journal Article · Tue Mar 01 04:00:00 EST 2016 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2016.02.015· OSTI ID:22746418

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

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. - Highlights: • Inhibition of p300 HAT in cultured palate cells increased E-cadherin expression. • Inhibition of p300 HAT perturbed canonical Wnt signaling in cultured palate cells. • Blocking p300 HAT in palate cells altered rates of apoptosis, proliferation, and migration.

• OSTI ID: 22746418
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1 Vol. 342; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
CELL PROLIFERATION
EMBRYOS
GENES
HISTONES
INHIBITION
MEMBRANES
MICE
MORPHOGENESIS
SIGNALS
TRANSCRIPTION
TRANSCRIPTION FACTORS