Transcriptional repression of the IMD2 gene mediated by the transcriptional co-activator Sub1

Transcriptional repression of the IMD2 gene mediated by the transcriptional co-activator Sub1
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DOI:
10.1111/j.1365-2443.2008.01229.x
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发表时间:
2008-11-01
期刊:
影响因子:
2.1
通讯作者:
Sekimizu, Kazuhisa
Sekimizu, Kazuhisa
中科院分区:
生物学4区
文献类型:
--
作者:
Koyama, Hiroshi;Sumiya, Eriko;Sekimizu, Kazuhisa

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Sub1最初被鉴定为转录辅激活因子,后来被证明在多个转录步骤中具有多效性功能,包括起始、延伸和终止。本研究揭示了Sub1作为芽殖酵母转录抑制因子的一种新功能。Sub1不激活IMP脱氢酶2(IMD 2)基因表达,而是抑制其表达。首先,我们研究了Sub1与转录延伸因子S-II/TFIIS(由DST 1基因编码)的遗传相互作用。干扰SUB1基因部分抑制敏感性的转录延伸抑制剂霉酚酸酯(MPA)在dst 1基因缺失突变体。SUB1基因缺失增加了IMD 2基因的表达水平,这赋予了对MPA的抗性,表明Sub1的功能是抑制IMD 2基因的表达。Sub1位于IMD 2基因启动子区附近。转录起始位点的上游区域是Sub1抑制IMD 2基因表达所必需的。这些结果表明,转录辅激活子Sub1也有在体内转录起始过程中的转录抑制的作用。
Sub1 was originally identified as a transcriptional co-activator and later demonstrated to have pleiotropic functions during multiple transcription steps, including initiation, elongation and termination. The present study reveals a novel function of Sub1 as a transcription repressor in budding yeast. Sub1 does not activate IMP dehydrogenase 2 (IMD2) gene expression but rather represses its expression. First, we examined the genetic interaction of Sub1 with the transcription elongation factor S-II/TFIIS, which is encoded by the DST1 gene. Disruption of the SUB1 gene partially suppressed sensitivity to the transcription elongation inhibitor mycophenolate (MPA) in a dst1 gene deletion mutant. SUB1 gene deletion increased the expression level of the IMD2 gene, which confers resistance to MPA, indicating that Sub1 functions to repress IMD2 gene expression. Sub1 located around the promoter region of the IMD2 gene. The upstream region of the transcription start sites was required for Sub1 to repress the IMD2 gene expression. These results suggest that the transcriptional co-activator Sub1 also has a role in transcriptional repression during transcription initiation in vivo.