Enhancer Codes with Ligand Mediated Gene Regulation and Chromatin Architecture

联系PD/PI：Nair，Sreejith Janardhanan 项目摘要 这项研究计划的中心目标是获得对细胞生物学原理的新见解 作为响应激素刺激的基因表达调节的基础。我的研究重点是基因 由转录增强子介导的调节。虽然被认为是基因的主要组织者， 在后生动物中的调控，增强子复合物组装和调节靶点的精确机制 对刺激作出反应的基因仍然是未知的。本提案中描述的初步数据表明， 强烈组装的增强子含有核糖核蛋白复合物，其物理化学性质相当 与组成型活性的增强子不同。一旦这些增强子被激活， 与染色质间颗粒（ICG）相关。该提案将把多种实验策略联系起来， 分子生物学、生物物理学、基因组学、蛋白质组学和显微镜学等多种学科， 全面了解诱导增强子激活和染色体 架构总之，这种方法可以显着改变我们目前对调控基因的概念， 转录程序。重要的是，从这项研究中获得的发现和实验技能也将使 过渡到学术生涯作为一个独立的研究者研究生物物理和分子 利用蛋白质组学、生物信息学和基因组学研究配体调控转录程序的机制 接近。 第6页 项目概要/摘要

Contact PD/PI: Nair, Sreejith Janardhanan PROJECT SUMMARY The central objective of this research proposal is to gain novel insights into the cell biological principles underlying the regulation of gene expression in response to hormonal stimulation. My research focus is gene regulation mediated by transcriptional enhancers. Although recognized as the major organizer of gene regulation in metazoans, the precise mechanism with which enhancer complex assembled and regulate target genes in response to stimuli is still mostly not known. Preliminary data described in this proposal suggest that acutely assembled enhancers harbor ribonucleoprotein complex with a physicochemical property that is quite distinct from that of enhancers that are constitutively active. These enhancers get optimally activated once associated with inter-chromatin granules (ICGs). This proposal will link multiple experimental strategies from disciplines as diverse as molecular biology, biophysics, genomics, proteomics and microscopy to provide a comprehensive understanding of the underlying mechanism of inducible enhancer activation and chromosomal architecture. Together, this approach can significantly alter our current concepts about regulated gene transcriptional programs. Importantly, the finding and experimental skills acquired from this study will also allow the transition to an academic career as an independent investigator studying the biophysical and molecular mechanisms of ligand regulated transcriptional program using proteomic, bioinformatics and genomic approaches. Page 6 Project Summary/Abstract