Disease relevance of HIR1

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

High impact information on HIR1

• Finally, CAF-I subunits and Hir1 are enriched at centromeres, indicating that these proteins make a direct contribution to centromeric chromatin structures [2].
• Promoter closure occurs very rapidly, and the histone chaperones Asf1 and Hir1 as well as the SWI/SNF nucleosome remodeling complex appear to be important for rapid reassembly of nucleosomes at the PHO5 promoter [3].
• The Hira gene encodes a nuclear WD40 domain protein homologous to the yeast transcriptional corepressors Hir1p and Hir2p [4].
• Tethered Hir1p also directed the periodic transcription of the HTA1 gene and repressed HTA1 transcription in response to two cell cycle regulatory signals [5].
• Hir1p and Hir2p function as transcriptional corepressors to regulate histone gene transcription in the Saccharomyces cerevisiae cell cycle [5].

Biological context of HIR1

• Deletion of either HIR1 or ASF1 eliminated telomeric gene silencing in combination with pol30--8, encoding an altered form of the DNA polymerase processivity factor PCNA that prevents CAF-I from contributing to silencing [6].
• The results suggest that ASF1 and HIR1 function in the same pathway to create a repressive chromatin structure in the histone genes during the cell cycle [7].
• Transcription analysis revealed that the expression of histone genes was lowered in the mutant over-expressing HIR1, indicating a relationship between the latter gene and apoptosis [8].
• The over-expression of HIR1 in the Kllsm4Delta1 mutant prevented rapid cell death during chronological aging, reduced nuclei fragmentation and increased resistance to H(2)O(2) [8].
• HIR1, the co-repressor of histone gene transcription of Saccharomyces cerevisiae, acts as a multicopy suppressor of the apoptotic phenotypes of the LSM4 mRNA degradation mutant [8].

Physical interactions of HIR1

• In this analysis, we show that HIR1 interacts with ASF1 in a two-hybrid analysis [7].

Other interactions of HIR1

• When Hir1p and Hir2p were artificially tethered to yeast promoters, each protein repressed transcription, suggesting that they represent a new class of transcriptional corepressors [5].
• In vivo, the HIR1 and ASF1 genes contributed to silencing the heterochromatic HML locus via the same genetic pathway [6].
• The sequence of the HIR1 gene predicts an 88-kDa protein with three repeats of a motif found in the G beta subunit of retinal transducin and in a yeast transcriptional repressor, Tup1 [9].
• The HIR1 and HIR2 genes have been isolated, and their roles in the transcriptional regulation of the HTA1-HTB1 locus have been characterized [9].

Analytical, diagnostic and therapeutic context of HIR1

• Functional dissection of yeast Hir1p, a WD repeat-containing transcriptional corepressor [10].

References