Horak Christine E, Luscombe Nicholas M, Qian Jiang, Bertone Paul, Piccirrillo Stacy, Gerstein Mark, Snyder Michael
Department of Molecular, Cellular, and Developmental Biology, Connecticut 06520-8103, USA.
Genes Dev. 2002 Dec 1;16(23):3017-33. doi: 10.1101/gad.1039602.
In the yeast Saccharomyces cerevisiae, SBF (Swi4-Swi6 cell cycle box binding factor) and MBF (MluI binding factor) are the major transcription factors regulating the START of the cell cycle, a time just before DNA replication, bud growth initiation, and spindle pole body (SPB) duplication. These two factors bind to the promoters of 235 genes, but bind less than a quarter of the promoters upstream of genes with peak transcript levels at the G1 phase of the cell cycle. Several functional categories, which are known to be crucial for G1/S events, such as SPB duplication/migration and DNA synthesis, are under-represented in the list of SBF and MBF gene targets. SBF binds the promoters of several other transcription factors, including HCM1, PLM2, POG1, TOS4, TOS8, TYE7, YAP5, YHP1, and YOX1. Here, we demonstrate that these factors are targets of SBF using an independent assay. To further elucidate the transcriptional circuitry that regulates the G1-to-S-phase progression, these factors were epitope-tagged and their binding targets were identified by chIp-chip analysis. These factors bind the promoters of genes with roles in G1/S events including DNA replication, bud growth, and spindle pole complex formation, as well as the general activities of mitochondrial function, transcription, and protein synthesis. Although functional overlap exists between these factors and MBF and SBF, each of these factors has distinct functional roles. Most of these factors bind the promoters of other transcription factors known to be cell cycle regulated or known to be important for cell cycle progression and differentiation processes indicating that a complex network of transcription factors coordinates the diverse activities that initiate a new cell cycle.
在酿酒酵母中，SBF（Swi4-Swi6细胞周期盒结合因子）和MBF（MluI结合因子）是调节细胞周期起始的主要转录因子，细胞周期起始发生在DNA复制、芽生长起始和纺锤体极体（SPB）复制之前。这两种因子与235个基因的启动子结合，但与细胞周期G1期转录水平峰值基因上游不到四分之一的启动子结合。几个已知对G1/S事件至关重要的功能类别，如SPB复制/迁移和DNA合成，在SBF和MBF基因靶标列表中的代表性不足。SBF与其他几个转录因子的启动子结合，包括HCM1、PLM2、POG1、TOS4、TOS8、TYE7、YAP5、YHP1和YOX1。在这里，我们使用独立检测方法证明这些因子是SBF的靶标。为了进一步阐明调节G1期到S期进程的转录调控网络，对这些因子进行了表位标签标记，并通过芯片免疫沉淀分析鉴定了它们的结合靶标。这些因子与在G1/S事件中发挥作用的基因启动子结合，包括DNA复制、芽生长和纺锤体复合体形成，以及线粒体功能、转录和蛋白质合成的一般活动。尽管这些因子与MBF和SBF之间存在功能重叠，但每个因子都有独特的功能作用。这些因子中的大多数与已知受细胞周期调控或已知对细胞周期进程和分化过程很重要的其他转录因子的启动子结合，这表明转录因子的复杂网络协调启动新细胞周期的各种活动。
