Role for Carbohydrate Response Element-Binding Protein (ChREBP) in High Glucose-Mediated Repression of Long Noncoding RNA Tug1

Authors

Jianyin Long
Daniel L Galvan
Koki Mise
Yashpal S Kanwar
Li Li
Naravat Poungavrin
Paul A Overbeek
Benny H Chang
Farhad R Danesh

Publication Date

11-20-2020

Journal

Journal of Biological Chemistry

DOI

10.1074/jbc.RA120.013228

PMID

32467232

PMCID

PMC7681008

PubMedCentral® Posted Date

5-28-2020

PubMedCentral® Full Text Version

Post-print

Published Open-Access

no

Keywords

Animals, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Cell Line, Tumor, Gene Expression Regulation, Glucose, Histone Deacetylase 1, Humans, Mice, Podocytes, RNA, Long Noncoding, Repressor Proteins, Transcription, Genetic

Abstract

Long noncoding RNAs (lncRNAs) have been shown to play key roles in a variety of biological activities of the cell. However, less is known about how lncRNAs respond to environmental cues and what transcriptional mechanisms regulate their expression. Studies from our laboratory have shown that the lncRNA Tug1 (taurine upregulated gene 1) is crucial for the progression of diabetic kidney disease, a major microvascular complication of diabetes. Using a combination of proximity labeling with the engineered soybean ascorbate peroxidase (APEX2), ChIP-qPCR, biotin-labeled oligonucleotide pulldown, and classical promoter luciferase assays in kidney podocytes, we extend our initial observations in the current study and now provide a detailed analysis on a how high-glucose milieu downregulates Tug1 expression in podocytes. Our results revealed an essential role for the transcription factor carbohydrate response element binding protein (ChREBP) in controlling Tug1 transcription in the podocytes in response to increased glucose levels. Along with ChREBP, other coregulators, including MAX dimerization protein (MLX), MAX dimerization protein 1 (MXD1), and histone deacetylase 1 (HDAC1), were enriched at the

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