Epigenetic control of skull morphogenesis by histone deacetylase 8.
Histone deacetylases (Hdacs) are transcriptional repressors with crucial roles in mammalian development. Here we provide evidence that Hdac8 specifically controls patterning of the skull by repressing a subset of transcription factors in cranial neural crest cells. Global deletion of Hdac8 in mice leads to perinatal lethality due to skull instability, and this is phenocopied by conditional deletion of Hdac8 in cranial neural crest cells. Hdac8 specifically represses the aberrant expression of homeobox transcription factors such as Otx2 and Lhx1. These findings reveal how the identity and patterning of vertebrate-specific portions of the skull are epigenetically controlled by a histone deacetylase.
Haberland
Michael
M
Department of Molecular Biology, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
Mokalled
Mayssa H
MH
Montgomery
Rusty L
RL
Olson
Eric N
EN
D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D044127:Epigenesis, Genetic; D017353:Gene Deletion; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006655:Histone Deacetylases / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D060850:LIM-Homeodomain Proteins; D051379:Mice; D051857:Otx Transcription Factors / Q000378:metabolism; D012886:Skull / Q000002:abnormalities / Q000196:embryology*; D014157:Transcription Factors
D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C499523:Lhx1 protein, mouse; D051857:Otx Transcription Factors; C497660:Otx2 protein, mouse; D014157:Transcription Factors; D006655:Histone Deacetylases