Enhancer Codes with Ligand Mediated Gene Regulation and Chromatin Architecture

联系PD/PI：Nair，Sreejith Janardhanan 项目总结 这项研究计划的中心目标是对细胞生物学原理有新的见解。 对荷尔蒙刺激作出反应的基因表达调控的基础。我的研究重点是基因 转录增强子介导的调控。尽管被认为是基因的主要组织者 后生动物中的调控，增强子复合体组装和调控靶标的精确机制 对刺激做出反应的基因大多仍不清楚。该提案中描述的初步数据表明， 急性组装的增强剂含有核糖核蛋白复合体，其物理化学性质相当 与天然活性的增强剂不同。一旦这些增强剂被激活，效果最佳 与染色质间颗粒(ICGS)相关。这项提案将把多个试验性战略从 不同学科，如分子生物学、生物物理学、基因组学、蛋白质组学和显微技术，提供 全面了解可诱导增强子激活和染色体的潜在机制 建筑。总而言之，这种方法可以显著改变我们目前对受调控基因的概念 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 向研究生物物理和分子的独立研究员的学术生涯过渡 蛋白质组、生物信息学和基因组学研究配体调控转录程序的机制 接近了。 第6页 项目摘要/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