Hirota Kouji, Hoffman Charles S, Shibata Takehiko, Ohta Kunihiro
Genetic Dynamics Research Unit-Laboratory, The Institute of Physical and Chemical Research (RIKEN), Wako-shi, Saitama 351-0198, Japan.
Genetics. 2003 Oct;165(2):505-15. doi: 10.1093/genetics/165.2.505.
Chromatin remodeling plays crucial roles in the regulation of gene expression and recombination. Transcription of the fission yeast fbp1(+) gene and recombination at the meiotic recombination hotspot ade6-M26 (M26) are both regulated by cAMP responsive element (CRE)-like sequences and the CREB/ATF-type transcription factor Atf1*Pcr1. The Tup11 and Tup12 proteins, the fission yeast counterparts of the Saccharomyces cerevisiae Tup1 corepressor, are involved in glucose repression of the fbp1(+) transcription. We have analyzed roles of the Tup1-like corepressors in chromatin regulation around the fbp1(+) promoter and the M26 hotspot. We found that the chromatin structure around two regulatory elements for fbp1(+) was remodeled under derepressed conditions in concert with the robust activation of fbp1(+) transcription. Strains with tup11delta tup12delta double deletions grown in repressed conditions exhibited the chromatin state associated with wild-type cells grown in derepressed conditions. Interestingly, deletion of rst2(+), encoding a transcription factor controlled by the cAMP-dependent kinase, alleviated the tup11delta tup12delta defects in chromatin regulation but not in transcription repression. The chromatin at the M26 site in mitotic cultures of a tup11delta tup12delta mutant resembled that of wild-type meiotic cells. These observations suggest that these fission yeast Tup1-like corepressors repress chromatin remodeling at CRE-related sequences and that Rst2 antagonizes this function.
染色质重塑在基因表达调控和重组过程中发挥着关键作用。裂殖酵母fbp1(+)基因的转录以及减数分裂重组热点ade6-M26(M26)处的重组均受环磷酸腺苷反应元件(CRE)样序列和CREB/ATF型转录因子Atf1*Pcr1的调控。Tup11和Tup12蛋白是酿酒酵母Tup1共抑制因子在裂殖酵母中的对应物,参与fbp1(+)转录的葡萄糖抑制作用。我们分析了Tup1样共抑制因子在fbp1(+)启动子和M26热点周围染色质调控中的作用。我们发现,在去抑制条件下,fbp1(+)两个调控元件周围的染色质结构与fbp1(+)转录的强烈激活协同重塑。在抑制条件下生长的tup11δtup12δ双缺失菌株表现出与在去抑制条件下生长的野生型细胞相关的染色质状态。有趣的是,编码受环磷酸腺苷依赖性激酶调控的转录因子的rst2(+)缺失,减轻了tup11δtup12δ在染色质调控方面的缺陷,但在转录抑制方面没有作用。tup11δtup12δ突变体有丝分裂培养物中M26位点的染色质类似于野生型减数分裂细胞的染色质。这些观察结果表明,这些裂殖酵母Tup1样共抑制因子在CRE相关序列处抑制染色质重塑,而Rst2拮抗这种功能。