THE MBF-ASSOCIATED COREPRESSOR NRM1 REPRESSES G1-SPECIFIC TRANSCRIPTION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 酵母中G1特异性转录依赖于SBF和MBF。我们已经确定了Nrm 1（MBF靶点1的负调节因子），作为MBF的稳定组分。NRM 1（YNR 009 w）是一个在G1期晚期表达的MBF调控基因，通过MBF与G1特异性启动子结合。从G1期退出后的转录抑制需要Nrm 1和MBF两者。Nrm 1的失活导致MBF调节的转录物的表达延长，并导致对羟基脲（HU）的抗性和增强的rad 53和mec 1相关致死性的旁路。稳定形式的Nrm 1的组成型表达抑制MBF靶标并导致HU敏感性。由MBF靶基因nrm 1+（SPBC16A3.07）编码的裂殖酵母同源物SpNrm 1与MBF靶基因结合并作为辅阻遏物。在这两种酵母中，MBF抑制G1期以外的G1特异性转录。当细胞退出G1期时，涉及Nrm 1与MBF结合的负反馈环导致转录抑制。

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. G1-specific transcription in yeast depends upon SBF and MBF. We have identified Nrm1 (Negative Regulator of MBF targets 1), as a stable component of MBF. NRM1 (YNR009w), an MBF-regulated gene expressed during late G1 phase, associates with G1-specific promoters via MBF. Transcriptional repression upon exit from G1 phase requires both Nrm1 and MBF. Inactivation of Nrm1 results in prolonged expression of MBF-regulated transcripts and leads to hydroxyurea (HU) resistance and enhanced bypass of rad53∆- and mec1∆-associated lethality. Constitutive expression of a stabilized form of Nrm1 represses MBF targets and leads to HU sensitivity. The fission yeast homolog SpNrm1, encoded by the MBF target gene nrm1+ (SPBC16A3.07), binds to MBF target genes and acts as a corepressor. In both yeasts, MBF represses G1-specific transcription outside of G1 phase. A negative feedback loop involving Nrm1 bound to MBF leads to transcriptional repression as cells exit G1 phase.