Genomic binding profiling of the fission yeast stress-activated MAPK Sty1 and the bZIP transcriptional activator Atf1 in response to H2O2.

Genomic binding profiling of the fission yeast stress-activated MAPK Sty1 and the bZIP transcriptional activator Atf1 in response to H2O2.
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DOI:
10.1371/journal.pone.0011620
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发表时间:
2010-07-16
期刊:
影响因子:
3.7
通讯作者:
Liu J
Liu J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Eshaghi M;Lee JH;Zhu L;Poon SY;Li J;Cho KH;Chu Z;Karuturi RK;Liu J

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已知进化上保守的MAPK Sty 1和bZIP转录激活因子Atf 1在S.粟酒然而,目前还不清楚是否所有的H2 O2诱导的基因直接调节Sty 1-Atf 1途径,并参与生长适应下H2 O2诱导的压力条件。在这里,我们提出的研究ChIP芯片映射的基因组结合位点Sty 1,Atf 1,和Atf 1的结合伙伴Pcr 1;全基因组的atf 1和pcr 1菌株在响应H2 O2的转录谱;和H2 O2条件下的生长适应性的表型评估90 Atf 1/Pcr 1结合或未结合的基因。ChIP芯片分析表明,Atf 1和Pcr 1结合位点在基因组中重叠,并组成性存在H2 O2胁迫前。另一方面,Sty 1募集主要发生在Atf 1/Pcr 1结合位点,并由H2 O2诱导。我们发现Atf 1/Pcr 1明显负责对H2 O2的高水平转录反应。此外,表型评估表明,在H2 O2诱导的基因中,Atf 1/Pcr 1结合的基因表现出更高的可能性,在胁迫条件下的生长适应性的功能要求比Atf 1/Pcr 1未结合的基因做。值得注意的是,我们发现,Atf 1/Pcr 1结合的基因,无论他们对H2 O2的反应性显示出很高的可能性,要求生长适应性。总之,我们对蛋白质结合位点的全球定位,全基因组转录谱分析和表型评估的分析提供了深入了解全球转录调控机制的Sty 1-Atf 1途径在响应H2 O2诱导的活性氧。
The evolutionally conserved MAPK Sty1 and bZIP transcriptional activator Atf1 are known to play a pivotal role in response to the reactive oxygen species in S. pombe. However, it is unclear whether all of the H2O2-induced genes are directly regulated by the Sty1-Atf1 pathway and involved in growth fitness under H2O2-induced stress conditions. Here we present the study on ChIP-chip mapping of the genomic binding sites for Sty1, Atf1, and the Atf1's binding partner Pcr1; the genome-wide transcriptional profiling of the atf1 and pcr1 strains in response to H2O2; and the phenotypic assessment of ∼90 Atf1/Pcr1-bound or unbound genes for growth fitness under H2O2 conditions. ChIP-chip analysis shows that Atf1 and Pcr1 binding sites are overlapped in the genome and constitutively present before H2O2 stress. On the other hand, Sty1 recruitment primarily occurs at the Atf1/Pcr1 binding sites and is induced by H2O2. We found that Atf1/Pcr1 is clearly responsible for the high-level transcriptional response to H2O2. Furthermore, phenotypic assessment indicates that among the H2O2-induced genes, Atf1/Pcr1-bound genes exhibit a higher likelihood of functional requirement for growth fitness under the stress condition than the Atf1/Pcr1-unbound genes do. Notably, we found that the Atf1/Pcr1-bound genes regardless of their responsiveness to H2O2 show a high probability of requirement for growth fitness. Together, our analyses on global mapping of protein binding sites, genome-wide transcriptional profiling, and phenotypic assessment provide insight into mechanisms for global transcriptional regulation by the Sty1-Atf1 pathway in response to H2O2-induced reactive oxygen species.
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作者:
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