GENETIC ANALYSIS OF CELL CYCLE-DEPENDENT TRANSCRIPTION

癌症的发生通常与未能调节 细胞周期处于G1期向S期过渡。此关键周期 这一事件与编码必需的基因的转录相吻合 染色体蛋白质，组蛋白。在这个转折点上，组蛋白 合成必须在时间和数量上进行调节，以确保 在细胞周期较晚的M期，染色体发生了忠实分离。 酵母组蛋白基因的转录模式已被利用来 识别在G1-S相界发挥作用的新的调控因子。 四个调控基因(hir、组蛋白调控)的突变已经被 目前已分离到3个野生型基因。每个人 突变通过影响细胞周期来降低转录水平 在组蛋白基因启动子的两个调控位置起作用的因子。一 一组基因(HIR1、HIR2、HIR3)编码的蛋白质可以 以抑制物为特征的，起负性作用的。其中两种蛋白质 (Hir1和Hir2)不直接接触DNA，假设他们 作为协同抑制因子的功能将得到测试。第四个基因的产物 (HIR4)作用于组蛋白特异性激活元件(UA)以缓解 负面网站的压抑。假设这种基因产物 作为反抑制器的功能将得到测试。 组蛋白合成的定量调控已被发现。 通过新的自我调节现象；组蛋白H_2A和H_2B 通过许多相同的基因来调节一个HTAHTB基因的转录 调节周期转录的因子。假设 自动调节是通过H_2A和HIR产物之间的相互作用来实现的 吉恩将接受测试。

Carcinogenesis is frequently associated with the failure to regulate the cell cycle at the transition from G1 into S phase. This key periodic event coincides with the transcription of genes that encode the essential chromosomal proteins, histones. At this transition point, histone synthesis must be regulated both temporally and quantitatively to ensure faithful chromosome segregation later in the cell cycle during M phase. The transcription pattern of yeast histone genes has been exploited to identify novel regulatory factors that act at the G1-S phase boundary. Mutations in four regulatory genes (HIR, histone regulation) have been identified, and three of the wild type genes have been isolated. Each mutation derepresses transcription during the cell cycle by affecting factors that act at two regulatory sites in a histone gene promoter. One group of genes (HIR1, HIR2, HIR3) encode proteins that can be characterized as repressors that act a negative site. Two of the proteins (Hir1 and Hir2) do not contact DNA directly, and the hypothesis that they function as co-repressors will be tested. The product of a fourth gene (HIR4) acts at the histone-specific activation elements (UAS) to relieve repression by the negative site. The hypothesis that this gene product functions as an anti-repressor will be tested. Quantitative regulation of histone synthesis has been found to occur through the novel phenomenon of autoregulation; histones H2A and H2B regulate transcription of one HTAHTB locus through many of the same factors that regulate periodic transcription. The hypothesis that autoregulation occurs by interaction between H2A and the product of a HIR gene will be tested.