Abstract
Gcn5 was the first transcription-related histone acetyltransferase (HAT) to be identified. However, the functions of this enzyme in mammalian cells remain poorly defined. Deletion of Gcn5 in mice leads to early embryonic lethality with increased apoptosis in mesodermal lineages. Here we show that deletion of p53 allows Gcn5-/- embryos to survive longer, but Gcn5-/- p53-/- embryos still die in midgestation. Interestingly, embryos homozygous for point mutations in the Gcn5 catalytic domain survive significantly longer than Gcn5-/- or Gcn5-/- p53 -/- mice. In contrast to Gcn5-/- embryos, Gcn5 hat/hat embryos do not exhibit increased apoptosis but do exhibit severe cranial neural tube closure defects and esencephaly. Together, our results indicate that Gcn5 has important, HAT-independent functions in early development and that Gcn5 acetyltransferase activity is required for cranial neural tube closure in the mouse.
Original language | English (US) |
---|---|
Pages (from-to) | 3405-3416 |
Number of pages | 12 |
Journal | Molecular and cellular biology |
Volume | 27 |
Issue number | 9 |
DOIs | |
State | Published - May 2007 |
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
MD Anderson CCSG core facilities
- Advanced Technology Genomics Core
- Genetically Engineered Mouse Facility