期刊
DEVELOPMENTAL DYNAMICS
卷 237, 期 4, 页码 928-940出版社
WILEY
DOI: 10.1002/dvdy.21479
关键词
histone; acetyltransferase; exencephaly; chromatin; embryo
资金
- NATIONAL CANCER INSTITUTE [P30CA016672] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM067718] Funding Source: NIH RePORTER
- NCI NIH HHS [CA16672, P30 CA016672] Funding Source: Medline
- NIGMS NIH HHS [R01 GM067718-05A1, R01GM067718, R01 GM067718] Funding Source: Medline
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 Gen5(flox(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 Gcn5(flox(neo)/Delta) 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.
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