EXPRELA Group, Departamento de Bioloxía, Centro de Investigacións Científicas Avanzadas (CICA), Facultade de Ciencias, Universidade da Coruña, Campus de A Zapateira, 15071, A Coruña 15001, Spain.
FEMS Yeast Res. 2018 Mar 1;18(2). doi: 10.1093/femsyr/foy013.
Ixr1 is a Saccharomyces cerevisiae transcriptional factor that extensively regulates the response to hypoxia and controls other important cellular functions and DNA repair. During aerobic growth, the Ixr1 repressor function is predominant on regulated promoters of hypoxic genes, although activator effects are also observed on other genes. During hypoxia, Ixr1 expression increases and the number of genes activated by Ixr1 also increase. In this work we demonstrate that the NH2-terminal region of Ixr1 is involved in transcriptional activation. We also present the first analysis about Ixr1 interactions with three factors that have been previously identified as important players in the yeast hypoxic response, Cyc8, Tup1 and Ssn8; results demonstrate that only Ssn8 binds to Ixr1. We have also looked for other Ixr1-binding proteins associated with transcriptional regulation, by co-purification and mass spectrometry identification. Tdh3, a protein involved in transcriptional silencing, is among the new identified Ixr1-binding proteins. Differential phosphorylation of Ixr1 is found when comparing aerobic and hypoxic yeast growth. Implication of these results in transcriptional regulation mediated by Ixr1 is discussed.
Ixr1 是酿酒酵母的一种转录因子，广泛调节对低氧的反应，并控制其他重要的细胞功能和 DNA 修复。在有氧生长过程中，Ixr1 抑制剂的功能主要在缺氧基因的调节启动子上起作用，尽管在其他基因上也观察到激活剂的作用。在低氧条件下，Ixr1 的表达增加，受 Ixr1 激活的基因数量也增加。在这项工作中，我们证明了 Ixr1 的 NH2-末端区域参与转录激活。我们还首次分析了 Ixr1 与之前被确定为酵母低氧反应中重要参与者的三个因子（Cyc8、Tup1 和 Ssn8）的相互作用，结果表明只有 Ssn8 与 Ixr1 结合。我们还通过共纯化和质谱鉴定寻找与转录调节相关的其他 Ixr1 结合蛋白。Tdh3，一种参与转录沉默的蛋白质，是新鉴定的 Ixr1 结合蛋白之一。在比较有氧和低氧酵母生长时，发现 Ixr1 的差异磷酸化。讨论了这些结果对 Ixr1 介导的转录调节的影响。
