The Forkhead transcription factor Hcm1 regulates chromosome segregation genes and fills the S-phase gap in the transcriptional circuitry of the cell cycle
The Forkhead transcription factor Hcm1 regulates chromosome segregation genes and fills the S-phase gap in the transcriptional circuitry of the cell cycle
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DOI：
10.1101/gad.1450606
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发表时间：
2006-08-15
影响因子：
10.5
通讯作者：
Breeden, Linda L.
中科院分区：
文献类型：
--
作者：
Pramila, Tata;Wu, Wei;Breeden, Linda L.
当细胞从细胞周期的一个阶段过渡到另一个阶段时，转录模式会发生巨大变化。为了更好地定义这种转录回路，我们收集了芽殖酵母整个细胞周期的新微阵列数据。这些数据与其他三个细胞周期数据集的组合分析确定了数百个新的高度周期性转录本，并提供每个转录本的加权平均峰值时间。利用这些数据和启动子序列的系统发育比较，我们鉴定了晚期S期特异性启动子元件。该元件是叉头蛋白 Hcm1 的结合位点，这是其细胞周期特异性活性所必需的。在含有保守 Hcm1 结合位点的细胞周期调控基因中，涉及染色体分离、纺锤体动力学和出芽的基因显着富集。这可以解释为什么 Hcm1 突变体的染色体丢失率高出 10 倍，并且需要纺锤体检查点来维持活力。 Hcm1 还诱导 M 期特异性转录因子 FKH1、FKH2 和 NDD1，以及两种细胞周期特异性转录抑制因子 WHI5 和 YHP1。因此，Hcm1 填补了我们对细胞周期转录回路理解的重大空白。
Transcription patterns shift dramatically as cells transit from one phase of the cell cycle to another. To better define this transcriptional circuitry, we collected new microarray data across the cell cycle of budding yeast. The combined analysis of these data with three other cell cycle data sets identifies hundreds of new highly periodic transcripts and provides a weighted average peak time for each transcript. Using these data and phylogenetic comparisons of promoter sequences, we have identified a late S-phase-specific promoter element. This element is the binding site for the forkhead protein Hcm1, which is required for its cell cycle-specific activity. Among the cell cycle-regulated genes that contain conserved Hcm1-binding sites, there is a significant enrichment of genes involved in chromosome segregation, spindle dynamics, and budding. This may explain why Hcm1 mutants show 10-fold elevated rates of chromosome loss and require the spindle checkpoint for viability. Hcm1 also induces the M-phase-specific transcription factors FKH1, FKH2, and NDD1, and two cell cycle-specific transcriptional repressors, WHI5 and YHP1. As such, Hcm1 fills a significant gap in our understanding of the transcriptional circuitry that underlies the cell cycle.