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Title:Role of JMJD3 Histone Demethylase in Hepatic Expression of TFEB, a Key Autophagy Gene Activator
Author(s):Kim, Giyeong
Contributor(s):Kemper, Jongsook Kim
Abstract:During periods of starvation, cells survive by minimizing energy spent on biomaterial synthesis and triggering catabolic pathways. This adaptation requires a process called autophagy, which is a regulated destructive mechanism by which cellular materials are transported to the lysosome for degradation and recycled for the energy use. It has long been reported that autophagy is regulated at the transcriptional level and involves the master regulator, Transcription Factor EB (TFEB). However, the precise mechanism of how TFEB genes are transcribed and regulated is relatively less understood. Here we show the TFEB gene is regulated by a histone demethylase, Jumonji_D3 (Jmjd3) interacting with peroxisome proliferator- activated receptor alpha (PPARα). We found by RNA sequencing data that Jmjd3 down- regulation in primary hepatocytes results in TFEB gene expression levels significantly reduced compared to control. Also in vivo, AAV-iCre JmjD3 treated Jmjd3 floxed mice to deleted the jmjd3 gene, resulted in an 85% TFEB RNA decrease in qRT-PCR assays. Our data suggests that by demethylating histones, Jmjd3 is involved in the regulation of TFEB. We anticipate our results to be a tool that can will better our understanding of the mechanism of autophagy in response to the cell’s nutrient availability.
Issue Date:2017
Genre:Dissertation / Thesis
Rights Information:Copyright 2017 Giyeong Kim
Date Available in IDEALS:2017-05-16

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