Universidade da Coruña, Grupo EXPRELA, Centro de Investigacións Científicas Avanzadas (CICA), Facultade de Ciencias, 15071 A, Coruña, Spain.
Sci Rep. 2018 Feb 15;8(1):3090. doi: 10.1038/s41598-018-21439-1.
Ixr1 is a Saccharomyces cerevisiae HMGB protein that regulates the hypoxic regulon and also controls the expression of other genes involved in the oxidative stress response or re-adaptation of catabolic and anabolic fluxes when oxygen is limiting. Ixr1 also binds with high affinity to cisplatin-DNA adducts and modulates DNA repair. The influence of Ixr1 on transcription in the absence or presence of cisplatin has been analyzed in this work. Ixr1 regulates other transcriptional factors that respond to nutrient availability or extracellular and intracellular stress stimuli, some controlled by the TOR pathway and PKA signaling. Ixr1 controls transcription of ribosomal RNAs and genes encoding ribosomal proteins or involved in ribosome assembly. qPCR, ChIP, and 18S and 25S rRNAs measurement have confirmed this function. Ixr1 binds directly to several promoters of genes related to rRNA transcription and ribosome biogenesis. Cisplatin treatment mimics the effect of IXR1 deletion on rRNA and ribosomal gene transcription, and prevents Ixr1 binding to specific promoters related to these processes.
Ixr1 是酿酒酵母的一种 HMGB 蛋白，它可以调节缺氧调控基因，还可以控制与氧化应激反应或在氧气有限时分解代谢和合成代谢通量重新适应相关的其他基因的表达。Ixr1 还可以与顺铂-DNA 加合物高亲和力结合，并调节 DNA 修复。本工作分析了在不存在或存在顺铂的情况下 Ixr1 对转录的影响。Ixr1 调节其他对营养物质可用性或细胞外和细胞内应激刺激有反应的转录因子，其中一些受 TOR 途径和 PKA 信号转导控制。Ixr1 控制核糖体 RNA 和编码核糖体蛋白的基因或参与核糖体组装的基因的转录。qPCR、ChIP 和 18S 和 25S rRNAs 测量证实了这一功能。Ixr1 直接结合到与 rRNA 转录和核糖体生物发生相关的几个基因的启动子上。顺铂处理模拟了 IXR1 缺失对 rRNA 和核糖体基因转录的影响，并阻止了 Ixr1 与这些过程相关的特定启动子结合。
