Proper expression of the Gcn5 histone acetyltransferase is required for neural tube closure in mouse embryos
Article first published online: 10 MAR 2008
Copyright © 2008 Wiley-Liss, Inc.
Volume 237, Issue 4, pages 928–940, April 2008
How to Cite
Lin, W., Zhang, Z., Srajer, G., Chen, Y. C., Huang, M., Phan, H. M. and Dent, S. Y.R. (2008), Proper expression of the Gcn5 histone acetyltransferase is required for neural tube closure in mouse embryos. Dev. Dyn., 237: 928–940. doi: 10.1002/dvdy.21479
- Issue published online: 19 MAR 2008
- Article first published online: 10 MAR 2008
- Manuscript Accepted: 22 JAN 2008
- NIH. Grant Numbers: R01GM067718, GM067718
- NCI. Grant Number: CA16672
Histone acetyltransferases (HATs) are important to gene activation, altering chromatin structures to facilitate association of transcription proteins with gene promoters. The functions of individual HATs in mammalian developmental are not well defined. Our previous studies demonstrated that Gcn5, a prototypical HAT, is required for mesodermal maintenance in early embryos. Homozygous Gcn5 null embryos die soon after gastrulation, preventing determination of Gcn5 functions later during development. We report here the creation of a Gcn5flox(neo) allele, which is only partially functional and gives rise to a hypomorphic phenotype. Mice homozygous for this allele had an increased risk of cranial neural tube closure defects (NTDs) and exencephaly. These defects were found at an even greater penetrance in Gcn5flox(neo)/Δ embryos. These results indicate that normal levels of Gcn5 expression are critical for neural tube closure in mice and predict that mutations in this HAT may be associated with increased risk of NTDs in humans. Developmental Dynamics 237:928–940, 2008. © 2008 Wiley-Liss, Inc.