Mechanism of Chromatin Accessibility, 3D Chromosome Organization, and Their Functions in Gene Regulation

项目摘要 亲本资助R35 GM139654的主要重点之一是研究其机制和 先锋因子功能(PFS)。先锋因子(PFS)可侵袭核小体并增加 染色质在其结合部位附近的可及性，因此在基因中发挥关键作用 监管。PFS的错误调控与癌症和发育性疾病高度相关。尽管 它们的基本功能、PFS侵袭核小体的机制及其在体内的作用 基因调控需要进一步阐明。尤其与该补充剂应用相关， 我们想要对先锋因素如何影响基因表达有一个定量的了解。 信号存在时的电平、噪声和动态。为此，我们计划 干扰先锋因子及其在单细胞基因表达中的影响 通过时间推移荧光成像。在这里，我们申请资金购买显微镜 这个系统允许我们进行长期的活细胞成像。这台设备将满足一项关键的 需要我的实验室，以及宾夕法尼亚州立大学的基因调控中心，我的实验室是它的一部分 的。

Project Summary One of the major focus of the parental grant, R35 GM139654, is to study the mechanism and function of pioneer factors (PFs). Pioneer factors (PFs) can invade nucleosome and increase chromatin accessibility near their binding sites and therefore play critical roles in gene regulation. Mis-regulation of PFs is highly linked to cancer and developmental disease. Despite their essential functions, the mechanism of nucleosome invasion by PFs and their function in gene regulation require further elucidation. Particularly relevant to this supplement application, we want to have a quantitative understanding of how pioneer factors affect gene expression level, noise, and dynamics in the presence of signaling. Towards this purpose, we plan to perturb pioneer factors and measure the consequences in gene expression in single cells through time-lapse fluorescence imaging. Here, we request funding to purchase a microscope system that allows us to perform long-term live cell imaging. This equipment will fulfill a critical need for my lab, as well as the Center of Gene Regulation at Penn State, which my lab is part of.