Enhancer Codes with Ligand Mediated Gene Regulation and Chromatin Architecture

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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.