Disease relevance of HIR2

• A human homolog of the S. cerevisiae HIR1 and HIR2 transcriptional repressors cloned from the DiGeorge syndrome critical region [1].

High impact information on HIR2

• Here we show that ectopic expression of HIRA, the likely human ortholog of two cell cycle-regulated repressors of histone gene transcription in yeast (Hir1p and Hir2p), represses transcription of histones and that this, in turn, triggers a concerted block of DNA synthesis [2].
• Hir1p and Hir2p function as transcriptional corepressors to regulate histone gene transcription in the Saccharomyces cerevisiae cell cycle [3].
• Also, Asf1p bound to the Hir1p and Hir2p proteins in vitro and in cell extracts [4].
• CKB2 is located on the right arm of chromosome XV between the HIR2 and WHI2 loci and has not been previously identified genetically [5].
• Slm9 is most similar to Hir2, the histone gene regulator in budding yeast [6].

Biological context of HIR2

• One such protein is human HIRA, the homologue of two cell cycle-regulated repressors of histone gene expression in Saccharomyces cerevisiae, Hir1p and Hir2p [7].
• Domains of highest conservation with Hir1 and Hir2 are encoded from exons 1-11 and 13-25, respectively [8].

Other interactions of HIR2

• When Hir1p and Hir2p were artificially tethered to yeast promoters, each protein repressed transcription, suggesting that they represent a new class of transcriptional corepressors [3].
• Furthermore, increased expression of genes encoding Asf1p, Hir1p, and Hir2p suppressed the apc5(CA) Ts- defect in a CAF-I-dependent manner [9].

References