MSA1 IS REQUIRED FOR PROPER TIMING OF G1-SPECIFIC TRANSCRIPTION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在萌芽酵母中，通过Cln3/Cyclin依赖的蛋白激酶介导的G(1)特异性基因的转录激活，在G(1)期促进细胞周期的启动。最近为揭示SCB结合因子(SBF)和MCB结合因子(MBF)的新的相互作用而进行的筛选发现，除了SBF特异的抑制子Whi5和MBF特异的辅阻遏子Nrm1外，还有一对同源蛋白Msa1和Msa2(由YOR066w和YKR077w编码)分别是SBF和MBF的相互作用因子。MSA1在细胞周期中周期性地表达，峰值mRNA水平出现在M/G(1)晚期，峰值蛋白水平出现在G(1)早期。MSA1与SBF和MBF调控的靶启动子相关，在G(1)特异性转录调控中起着一致的作用。MSA1通过提前G(1)特异性基因的转录时间来影响细胞周期的启动。MSA1与SBF和MBF调节的启动子结合，在G(1)期结合最大。结合依赖于同源转录因子。MSA1的过度表达提前了SBF依赖的转录和发芽的时间，而耗尽则推迟了细胞周期启动的这两个指标。在MBF调控的转录中也观察到了类似的效果。根据这些结果，我们得出结论，MSA1可以提前G(1)特异性转录和细胞周期启动的时间。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In the budding yeast Saccharomyces cerevisiae, cell cycle initiation is prompted during G(1) phase by Cln3/cyclin-dependent protein kinase-mediated transcriptional activation of G(1)-specific genes. A recent screening performed to reveal novel interactors of SCB-binding factor (SBF) and MCB-binding factor (MBF) identified, in addition to the SBF-specific repressor Whi5 and the MBF-specific corepressor Nrm1, a pair of homologous proteins, Msa1 and Msa2 (encoded by YOR066w and YKR077w), as interactors of SBF and MBF, respectively. MSA1 is expressed periodically during the cell cycle with peak mRNA levels occurring at the late M/early G(1) phase and peak protein levels occurring in early G(1). Msa1 associates with SBF- and MBF-regulated target promoters consistent with a role in G(1)-specific transcriptional regulation. Msa1 affects cell cycle initiation by advancing the timing of transcription of G(1)-specific genes. Msa1 binds to SBF- and MBF-regulated promoters and binding is maximal during the G(1) phase. Binding depends upon the cognate transcription factor. Msa1 overexpression advances the timing of SBF-dependent transcription and budding, whereas depletion delays both indicators of cell cycle initiation. Similar effects on MBF-regulated transcription are observed. Based upon these results, we conclude that Msa1 acts to advance the timing of G(1)-specific transcription and cell cycle initiation.