INBRE-2 REGULATION OF COPPER HOMEOSTASIS IN YEAST

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 适当的铜稳态对于生命是必不可少的，并且所有细胞通过诱导转录程序来响应有毒的铜过量或铜饥饿，所述转录程序将导致过量铜的螯合或细胞外铜的摄取（根据需要）。过量的游离铜离子导致活性氧物质（ROS）的产生。 ROS是细胞大分子（包括DNA）损伤的主要来源。酵母CUP 1基因编码一种铜结合金属硫蛋白，该蛋白是在有毒铜水平存在下生存所必需的。CUP 1的诱导需要铜敏感激活剂Ace 1和染色质重塑剂SWI/SNF，并且CUP 1启动子受到动态组蛋白乙酰化的影响。 CUP 1转录在初始铜反应后也迅速关闭。这种自动调节是一个主动过程，不仅涉及Ace 1的释放，还涉及SWI/SNF的持续存在。我们还鉴定了CUP 1反义转录物RUF 5，其在CUP 1关闭期间转录。本研究的目的是了解染色质结构和修饰如何调节CUP 1转录周期，并探讨RUF 5转录本在CUP 1表达中的作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Proper copper homeostasis is essential for life, and all cells respond to toxic copper excess or copper starvation by inducing transcriptional programs that will result in sequestration of excess copper or uptake of extracellular copper, as needed. Excess free copper ions result in generation of reactive oxygen species (ROS). ROS are a major source of damage to cellular macromolecules, including DNA. The yeast CUP1 gene encodes a copper-binding metallothionein that is required for survival in the presence of toxic copper levels. CUP1 induction requires the copper-sensing activator Ace1 and the chromatin remodeler SWI/SNF, and the CUP1 promoter is subject to dynamic histone acetylation. CUP1 transcription is also rapidly shut down after the initial copper response. This autoregulation is an active process, which involves not only release of Ace1 but also the continued presence of SWI/SNF. We have also identified a CUP1 antisense transcript, RUF5, which is transcribed during CUP1 shutdown. The goal of this study is to understand how chromatin structure and modification regulate the CUP1 transcription cycle, and to explore the role of the RUF5 transcript in CUP1 expression.