Spector M S, Raff A, DeSilva H, Lee K, Osley M A
Program in Molecular Biology, Sloan Kettering Cancer Center, New York, New York 10021, USA.
Mol Cell Biol. 1997 Feb;17(2):545-52. doi: 10.1128/MCB.17.2.545.
The HIR/HPC (histone regulation/histone periodic control) negative regulators play important roles in the transcription of six of the eight core histone genes during the Saccharomyces cerevisiae cell cycle. The phenotypes of hir1 and hir2 mutants suggested that the wild-type HIR1 and HIR2 genes encode transcriptional repressors that function in the absence of direct DNA binding. When Hir1p and Hir2p were artificially tethered to yeast promoters, each protein repressed transcription, suggesting that they represent a new class of transcriptional corepressors. The two proteins might function as a complex in vivo: Hir2p required both Hir1p and another Hir protein, Hir3p, to repress transcription when it was tethered to an HTA1-lacZ reporter gene, and Hir1p and Hir2p could be coimmunoprecipitated from yeast cell extracts. Tethered Hir1p also directed the periodic transcription of the HTA1 gene and repressed HTA1 transcription in response to two cell cycle regulatory signals. Thus, it represents the first example of a transcriptional corepressor with a direct role in cell cycle-regulated transcription.
组蛋白调控/组蛋白周期控制（HIR/HPC）负调控因子在酿酒酵母细胞周期中，对八个核心组蛋白基因中的六个基因的转录起着重要作用。hir1和hir2突变体的表型表明，野生型HIR1和HIR2基因编码的转录抑制因子在没有直接DNA结合的情况下发挥作用。当Hir1p和Hir2p被人工连接到酵母启动子上时，每种蛋白质都会抑制转录，这表明它们代表了一类新的转录共抑制因子。这两种蛋白质可能在体内以复合物的形式发挥作用：当Hir2p连接到HTA1-lacZ报告基因上时，它需要Hir1p和另一种Hir蛋白Hir3p来抑制转录，并且Hir1p和Hir2p可以从酵母细胞提取物中进行共免疫沉淀。连接的Hir1p还指导HTA1基因的周期性转录，并响应两个细胞周期调节信号抑制HTA1转录。因此，它代表了在细胞周期调控转录中起直接作用的转录共抑制因子的第一个例子。
