title: A human homolog of the S. cerevisiae HIR1 and HIR2 transcriptional repressors cloned from the DiGeorge syndrome critical region.
abstract: The DiGeorge syndrome (DGS) is a developmental disorder affecting derivatives of the third and fourth pharyngeal pouches. DGS patients present an interstitial deletion in one of their two chromosomes 22. Cosmid DAC30 was mapped to the DGS smallest critical region. Iterative cDNA library screening initiated with a DAC30 gene fragment candidate yielded a cDNA contig whose assembled nucleotide sequence is consistent with the widely transcribed, 4.2-4.4 kb long, messengers detected by northern analysis. The deduced protein sequence, 1017 amino acids in length, entirely encompasses the 766 amino acids previously designated as TUPLE1. The completed protein has been renamed HIRA because it contains various features matching those found in HIR1 and HIR2, two repressors of histone gene transcription characterized in the yeast Saccharomyces cerevisiae. Strikingly alike in their N-terminal third, HIRA and HIR1 contain seven copies of the WD repeat, a motif implicated in protein-protein interactions, suggesting that they might define a new subfamily of functionally homologous proteins. The remainder of the human polypeptide highly resembles a corresponding fragment in HIR2. We propose that HIRA, alone, could have a part in mechanisms of transcriptional regulation similar to that played by HIR1 and HIR2 together. The presence of a single copy of the HIRA gene in DGS patients possibly accounts for some of the abnormalities associated with this syndrome.
authors.affiliation: Laboratoire de Biologie des Tumeurs Humaines, CNRS URA 1156, Institut Gustave Roussy, Villejuif, France.
authors.forename: V
authors.initials: V
authors.lastname: Lamour
authors.forename: Y
authors.initials: Y
authors.lastname: Lécluse
authors.forename: C
authors.initials: C
authors.lastname: Desmaze
authors.forename: M
authors.initials: M
authors.lastname: Spector
authors.forename: M
authors.initials: M
authors.lastname: Bodescot
authors.forename: A
authors.initials: A
authors.lastname: Aurias
authors.forename: M A
authors.initials: MA
authors.lastname: Osley
authors.forename: M
authors.initials: M
authors.lastname: Lipinski
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D018797:Cell Cycle Proteins; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004062:DiGeorge Syndrome / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics; D056488:Histone Chaperones; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D005656:Fungal Proteins; C078808:HIR1 protein, S cerevisiae; C078809:HIR2 protein, S cerevisiae; C086057:HIRA protein, human; D056488:Histone Chaperones; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors