Constraining G1-specific transcription to late G1 phase: The MBF-associated corepressor Nrm1 acts via negative feedback

被引:108
作者
de Bruin, Robertus A. M.
Kalashnikova, Tatyana I.
Chahwan, Charly
Hayes McDonald, W.
Wohlschlegel, James
Yates, John, III
Russell, Paul
Wittenberg, Curt
机构
[1] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA
[2] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
关键词
D O I
10.1016/j.molcel.2006.06.025
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:483 / 496
页数:14
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