Constraining G1-specific transcription to late G1 phase: The MBF-associated corepressor Nrm1 acts via negative feedback
Constraining G1-specific transcription to late G1 phase: The MBF-associated corepressor Nrm1 acts via negative feedback
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DOI：
10.1016/j.molcel.2006.06.025
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发表时间：
2006-08-18
期刊：
影响因子：
16
通讯作者：
Wittenberg, Curt
中科院分区：
文献类型：
--
作者：
de Bruin, Robertus A. M.;Kalashnikova, Tatyana I.;Wittenberg, Curt
酵母中G1特异性转录依赖于SBF和MBF。我们已经确定Nrm1（负调节MBF目标1），作为一个稳定的组成部分MBF。NRM1（YNR009w）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Nrml和MBF两者。Nrml的失活导致MBF调节的转录物的延长表达，并导致对羟基脲（HU）的抗性和增强的rad53 Delta和mec1 Delta相关致死性的旁路。稳定形式的Nrml的组成型表达抑制MBF靶标并导致HU敏感性。由MBF靶基因nrm1（+）（SPBC16A3.07c）编码的裂殖酵母同源物SpNrm1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，涉及与MBF结合的Nrml的负反馈环导致转录抑制。
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 Nrml and MBF. Inactivation of Nrml results in prolonged expression of MBF-regulated transcripts and leads to hydroxyurea (HU) resistance and enhanced bypass of rad53 Delta- and mec1 Delta-associated lethality. Constitutive expression of a stabilized form of Nrml represses MBF targets and leads to HU sensitivity. The fission yeast homolog SpNrm1, encoded by the MBF target gene nrm1(+) (SPBC16A3.07c), 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 Nrml bound to MBF leads to transcriptional repression as cells exit G1 phase.