Proper Gcn5 histone acetyltransferase expression is required for normal anteroposterior patterning of the mouse skeleton.
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)/Delta) 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.
Lin
Wenchu
W
Program in Genes and Development, and Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Zhang
Zhijing
Z
Chen
Chih-Hsin
CH
Behringer
Richard R
RR
Dent
Sharon Y R
SY
D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D001842:Bone and Bones / Q000196:embryology* / Q000201:enzymology*; D002843:Chromatin / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D051548:Histone Acetyltransferases / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D006657:Histones / Q000378:metabolism; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D009154:Mutation; D050880:p300-CBP Transcription Factors / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D000099224:p300-CBP-Associated Factor
D002843:Chromatin; D051548:Histone Acetyltransferases; D006657:Histones; D018398:Homeodomain Proteins; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor