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Proper Gcn5 histone acetyltransferase expression is required for normal anteroposterior patterning of the mouse skeleton
Author(s) -
Lin Wenchu,
Zhang Zhijing,
Chen ChihHsin,
Behringer Richard R.,
Dent Sharon Y. R.
Publication year - 2008
Publication title -
development, growth and differentiation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 66
eISSN - 1440-169X
pISSN - 0012-1592
DOI - 10.1111/j.1440-169x.2008.01041.x
Subject(s) - biology , homeotic gene , neural tube , hox gene , gastrulation , genetics , microbiology and biotechnology , anatomy , embryogenesis , transcription factor , embryo , gene
Histone acetylation plays important roles in gene regulation. However, the functions of individual histone acetyltransferases (HATs) in specific developmental transcription programs are not well defined. To define the functions of Gcn5, a prototypical HAT, during mouse development, we have created a series of mutant Gcn5 alleles. Our previous work revealed that deletion of Gcn5 leads to embryonic death soon after gastrulation. Embryos homozygous for point mutations in the catalytic center of Gcn5 survive longer, but die soon after E16.0 and exhibit defects in cranial neural tube closure. Embryos bearing a hypomorphic Gcn5 flox(neo) allele also exhibit neural closure defects and die at or soon after birth. We report here that Gcn5 flox(neo)/flox(neo) and Gcn5 flox(neo)/Δ embryos exhibit anterior homeotic transformations in lower thoracic and lumbar vertebrae. These defects are accompanied by a shift in the anterior expression boundary of Hoxc8 and Hoxc9 . These data provide the first evidence that Gcn5 contributes to Hox gene regulation and is required for normal anteroposterior patterning of the mouse skeleton.