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将G1期特异性转录限制在G1晚期:与MBF相关的共抑制因子Nrm1通过负反馈发挥作用。

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

作者信息

de Bruin Robertus A M, Kalashnikova Tatyana I, Chahwan Charly, McDonald W Hayes, Wohlschlegel James, Yates John, Russell Paul, Wittenberg Curt

机构信息

Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.

出版信息

Mol Cell. 2006 Aug;23(4):483-96. doi: 10.1016/j.molcel.2006.06.025.

Abstract

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 rad53Delta- and mec1Delta-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(+) (SPBC16A3.07c), 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 Nrm1 bound to MBF leads to transcriptional repression as cells exit G1 phase.

摘要

酵母中的G1期特异性转录依赖于SBF和MBF。我们已鉴定出Nrm1(MBF靶标1的负调控因子)是MBF的一个稳定成分。NRM1(YNR009w)是一个在G1期晚期表达的受MBF调控的基因,它通过MBF与G1期特异性启动子结合。从G1期退出时的转录抑制需要Nrm1和MBF两者。Nrm1的失活导致MBF调控转录本的持续表达,并导致对羟基脲(HU)产生抗性,以及增强对与rad53Δ和mec1Δ相关的致死性的绕过。稳定形式的Nrm1的组成型表达会抑制MBF靶标,并导致对HU敏感。由MBF靶标基因nrm1⁺(SPBC16A3.07c)编码的裂殖酵母同源物SpNrm1与MBF靶标基因结合,并作为一个共抑制因子发挥作用。在这两种酵母中,MBF在G1期之外抑制G1期特异性转录。当细胞退出G1期时,一个涉及与MBF结合的Nrm1的负反馈环导致转录抑制。

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