Genomes and Genes
Function and specificity of thiazolinedione induced eRNAs
Principal Investigator: Jill M Marinis
Abstract: DESCRIPTION (provided by applicant): The nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPAR?) is a master regulator of adipogenesis and metabolism. The widely used anti-diabetic class of thiazolinedione (TZD) drugs target PPAR? to decrease circulating levels of glucose, insulin, triglycerides, and free fatty acids;however, te molecular mechanisms and cell targets of these actions are not completely understood. We have employed a novel genome-wide technique, Global Run-On Sequencing (GRO-seq) to identify TZD-induced long non- coding RNAs (lncRNA) from PPAR? bound enhancers, (eRNAs), in adipocytes. We hypothesize that eRNAs mediate PPAR? expression profiles in adipocytes and dictate cell-specific TZD-induced gene expression networks. The first aim of this proposal is dedicated to determining the physiological significance and mechanism of action of eRNAs in adipocytes. Both global and individual functions of eRNAs will be tested in experiments using RNAse or eRNA knockdown and overexpression. The second aim uses GRO-seq to identify eRNAs in macrophages. GRO-seq datasets of adipocytes and macrophages will be compared to identify cell type specific eRNAs. Identification of novel adipocyte specific factors and understanding their mechanism of action has the potential of tailoring therapeutics for cell specific actions to minimize adverse side-effects of TZDs.
Funding Period: 2013-07-01 - 2016-06-30
more information: NIH RePORT
- DIABETES AND ENDOCRINOLOGY RESEARCH CENTERDomenico Accili; Fiscal Year: 2013....
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- Transcriptional role of TLE3 in brown adipose tissue development and metabolismClaudio J Villanueva; Fiscal Year: 2013..The proposed studies are a logical transition from my postdoctoral studies in adipogenesis to the burgeoning field of brown adipocyte biology. ..
- NUCLEAR HORMONE RECEPTORS IN ADIPOCYTE DIFFERENTIATIONMitchell A Lazar; Fiscal Year: 2013..Our innovative approach will elucidate mechanisms underlying target gene- and tissue-specificity of PPAR?, which can be translated to the design of more selective insulin sensitizers to combat the epidemic of metabolic disorders. ..
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- Role of NCoR in Adipose TissueMaryam Ahmadian; Fiscal Year: 2013..abstract_text> ..
- A novel axis regulates adipocyte plasticitySean Hartig; Fiscal Year: 2013..I anticipate that my studies will provide new clues into the complex regulatory networks controlling energy balance in fat cells. If my hypothesis is true, the Ubc9/miR-30a axis might be exploited in novel therapies to manage T2DM. ..
- Vanderbilt Diabetes Research CenterAlvin C Powers; Fiscal Year: 2013..Because of the VDRTC and the environment it creates, VDRTC-affiliated investigators have made important scientific contributions related to diabetes, obesity, and metabolism. ..
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- Gene Networks controlling macrophage-adipocyte interactions in insulinChristopher K Glass; Fiscal Year: 2013..abstract_text> ..