Silent Chromatin Mechanisms

智力优势。 在真核细胞中，基因组被组织成称为染色质的DNA/蛋白质复合物。 染色质有两种形式，常染色质和异染色质。“区分它们的是与每种类型相关的蛋白质的身份。 常染色质通常含有活性表达基因（例如，那些是ON的），而异染色质通常含有失活基因（即，那些关闭的，沉默的）。 这个项目将探索位于异染色质中的基因的分子基础，因此通常是沉默的，被打开（例如，变得"转录激活"）以响应诸如高温或暴露于有毒化学品的应激。 该项目将利用酵母遗传学的力量，结合分子生物学和生物化学的现代技术。 以前的研究结果表明，异染色质中的基因与常染色质中的基因以一种根本不同的方式被激活，基于这些结果，该项目将为这一惊人的二分法提供重要的机制见解。 该项目将为博士后研究科学家提供培训。 从科学的角度来看，关于异染色质基因如何在酵母中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.