4.8 Article

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

期刊

MOLECULAR CELL
卷 23, 期 4, 页码 483-496

出版社

CELL PRESS
DOI: 10.1016/j.molcel.2006.06.025

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资金

  1. NCI NIH HHS [CA77325] Funding Source: Medline
  2. NCRR NIH HHS [P4 1RR11823] Funding Source: Medline
  3. NIGMS NIH HHS [GM059441, GM59447] Funding Source: Medline

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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.

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