Silent Chromatin Mechanisms

知识价值。在真核细胞中，基因组被组织成称为染色质的DNA/蛋白质复合体。染色质可以以两种形式存在，称为“常染色质”和“异染色质”。区别它们的是与每种类型相关的蛋白质的特性。常染色质通常包含积极表达的基因（例如，那些是ON的），而异染色质通常包含不活跃的基因（例如，那些是OFF的，沉默的）。该项目将探索位于异染色质上的基因的分子基础，这些基因通常是沉默的，如何在高温或暴露于有毒化学物质等压力下被打开（例如，变得“转录激活”）。该项目将利用酵母遗传学的力量与分子生物学和生物化学的现代技术相结合。先前的研究结果表明，异染色质中基因的激活方式与常染色质中基因的激活方式根本不同，在此基础上，该项目将为这一惊人的二分法提供重要的机制见解。更广泛的影响。本项目将培养一名博士后科研人员。从科学的角度来看，关于酵母中异色基因如何被激活的见解可能对其他真核生物的调控产生广泛的影响。

Intellectual Merit. In eukaryotic cells, the genome is organized into a DNA/protein complex called chromatin. Chromatin can exist in two forms, termed "euchromatin" and "heterochromatin." What distinguishes them is the identity of the proteins that are associated with each type. Euchromatin typically contains actively expressing genes (e.g., those that are ON), while heterochromatin typically contains inactive genes (i.e., those that are OFF, silent). This project will explore the molecular basis for how genes that are located in heterochromatin, and are therefore normally silent, get turned ON (e.g., become "transcriptionally activated") in response to stresses such as high temperature or exposure to toxic chemicals. The project will use the power of yeast genetics combined with the modern techniques of molecular biology and biochemistry. Building on previous results that suggested genes in heterochromatin are activated in a fundamentally different way than genes in euchromatin, this project will provide important mechanistic insights into this striking dichotomy.Broader Impacts. This project will provide training for a postdoctoral research scientist. From the scientific perspective, insights obtained about how heterochromatic genes are activated in yeast could have wide-ranging impacts on regulation in other eukaryotic organisms.