title: The murine homologue of HIRA, a DiGeorge syndrome candidate gene, is expressed in embryonic structures affected in human CATCH22 patients.
abstract: A wide spectrum of birth defects is caused by deletions of the DiGeorge syndrome chromosomal region at 22q11. Characteristic features include cranio-facial, cardiac and thymic malformations, which are thought to arise form disturbances in the interactions between hindbrain neural crest cells and the endoderm of the pharyngeal pouches. Several genes have been identified in the shortest region of deletion overlap at 22q11, but nothing is known about the expression of these genes in mammalian embryos. We report here the isolation of several murine embryonic cDNAs of the DiGeorge syndrome candidate gene HIRA. We identified several alternatively spliced transcripts. Sequence analysis reveals that Hira bears homology to the p60 subunit of the human Chromatin Assembly Factor I and yeast hir1p and Hir2p, suggesting that Hira might have some role in chromatin assembly and/or histone regulation. Whole mount in situ hybridization of mouse embryos at various stages of development show that Hira is ubiquitously expressed. However, higher levels of transcripts are detected in the cranial neural folds, frontonasal mass, first two pharyngeal arches, circumpharyngeal neural crest and the limb buds. Since many of the structures affected in DiGeorge syndrome derive from these Hira expressing cell populations we propose that haploinsufficiency of HIRA contributes to at least some of the features of the DiGeorge phenotype.
authors.affiliation: Institute of Pediatric Surgery, Erasmus University, Rotterdam, The Netherlands.
authors.forename: L G
authors.initials: LG
authors.lastname: Wilming
authors.forename: C A
authors.initials: CA
authors.lastname: Snoeren
authors.forename: A
authors.initials: A
authors.lastname: van Rijswijk
authors.forename: F
authors.initials: F
authors.lastname: Grosveld
authors.forename: C
authors.initials: C
authors.lastname: Meijers
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001934:Branchial Region / Q000378:metabolism; D018797:Cell Cycle Proteins; D056504:Chromatin Assembly Factor-1; D002868:Chromosomal Proteins, Non-Histone; D002869:Chromosome Aberrations / Q000235:genetics*; D025063:Chromosome Disorders; D002892:Chromosomes, Human, Pair 22; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000235:genetics; D004062:DiGeorge Syndrome / Q000235:genetics*; D004622:Embryo, Mammalian / Q000378:metabolism; D005091:Exons; D005260:Female; D005775:Gastrula; D015870:Gene Expression; D056488:Histone Chaperones; D006801:Humans; D018878:Limb Buds / Q000378:metabolism; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009432:Neural Crest / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C533593:CHAF1B protein, human; D018797:Cell Cycle Proteins; C533594:Chaf1b protein, mouse; D056504:Chromatin Assembly Factor-1; D002868:Chromosomal Proteins, Non-Histone; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C086057:HIRA protein, human; C484187:Hira protein, mouse; D056488:Histone Chaperones; D009687:Nuclear Proteins; D014157:Transcription Factors