Histone acetylation of glucose-induced thioredoxin-interacting protein gene expression in pancreatic islets

Show full item record



Permalink

http://hdl.handle.net/10138/231342

Citation

Bompada , P , Atac , D , Luan , C , Andersson , R , Omella , J D , Laakso , E O , Wright , J , Groop , L & De Marinis , Y 2016 , ' Histone acetylation of glucose-induced thioredoxin-interacting protein gene expression in pancreatic islets ' , International Journal of Biochemistry & Cell Biology , vol. 81 , pp. 82-91 . https://doi.org/10.1016/j.biocel.2016.10.022

Title: Histone acetylation of glucose-induced thioredoxin-interacting protein gene expression in pancreatic islets
Author: Bompada, Pradeep; Atac, David; Luan, Cheng; Andersson, Robin; Omella, Judit Domenech; Laakso, Emilia Ottosson; Wright, Jason; Groop, Leif; De Marinis, Yang
Other contributor: University of Helsinki, Institute for Molecular Medicine Finland

Date: 2016-12
Language: eng
Number of pages: 10
Belongs to series: International Journal of Biochemistry & Cell Biology
ISSN: 1357-2725
DOI: https://doi.org/10.1016/j.biocel.2016.10.022
URI: http://hdl.handle.net/10138/231342
Abstract: Thioredoxin-interacting protein (TXNIP) has been shown to be associated with glucose-induced deterioration of pancreatic beta cell function in diabetes. However, whether epigenetic mechanisms contribute to the regulation of TXNIP gene expression by glucose is not clear. Here we studied how glucose exerts its effect on TXNIP gene expression via modulation of histone acetylation marks. To achieve this, we applied clustered regularly interspaced short palindromic repeats/Cas9 (CRISPR/Cas9) to knock out his tone acetyltransferase (HAT) p300 in a rat pancreatic beta cell line INS1 832/13. We also treated the cells and human islets with chemical inhibitors of HAT p300 and histone deacetylase (HDAC). In human islets, diabetes and high glucose resulted in elevated TXNIP and EP300 expression, and glucose-induced TXNIP expression could be reversed by p300 inhibitor C646. In INS1 832/13 cells, Ep300 knock-out by CRISPR/Cas9 elevated glucose-induced insulin secretion and greatly reduced glucose-stimulated Txnip expression and cell apoptosis. This effect could be ascribed to decrease in histone marks H3K9ac and H4ac at the promoter and first coding region of the Txnip gene. Histone marks H3K9ac and H4ac in the Txnip gene in the wild-type cells was inhibited by HDAC inhibitor at high glucose, which most likely was due to enhanced acetylation levels of p300 after HDAC inhibition; and thereby reduced p300 binding to the Txnip gene promoter region. Such inhibition was absent in the Ep300 knock-out cells. Our study provides evidence that histone acetylation serves as a key regulator of glucose-induced increase in TXNIP gene expression and thereby glucotoxicity-induced apoptosis. (C) 2016 Elsevier Ltd. All rights reserved.
Subject: Glucotoxicity
Beta cell
Histone acetylation
Histone acetyltransferase p300
Histone deacetylase
Thioredoxin-interacting protein
BETA-CELL APOPTOSIS
CARBOHYDRATE RESPONSE ELEMENT
EPIGENETIC REGULATION
INSULIN-SECRETION
P300
TRANSCRIPTION
GENOME
TXNIP
AUTOACETYLATION
INVOLVEMENT
3111 Biomedicine
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
1_s2.0_S1357272516303296_main.pdf 2.187Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record