Affiliation:
1. Department of Biochemistry and Molecular Biology
2. Program in Genes and Development
3. Department of Cancer Genetics, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030
Abstract
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 exencephaly. 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.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Cited by
112 articles.
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