Dysregulated Lysine Acetyltransferase 2B Promotes Inflammatory Bowel Disease Pathogenesis Through Transcriptional Repression of Interleukin-10

Journal of Crohn's & Colitis
Alfa H C BaiSiew C Ng

Abstract

Accumulating evidence supports epigenetic modifications in mediating intestinal immunity in inflammatory bowel disease [IBD] pathogenesis. This study aimed to identify key dysregulated epigenetic modulators and the molecular downstream pathways in IBD. Expression of 116 well-defined epigenetic modulators was profiled and validated in 96 intestinal tissues from patients with Crohn's disease [CD], ulcerative colitis [UC], and healthy controls using quantitative reverse transcriptase polymerase chain reaction [QRT-PCR], western blot, and immunohistochemistry. Dysregulation of histone modifications and IBD-related cytokines were examined by chromatin immunoprecipitation, luciferase activity, and gene expression analyses in normal colonic epithelial cell line, NCM460, upon small-molecule inhibition or RNA interference, followed by validation in primary colonic tissues. Targeted expression profiling uncovered seven differentially expressed epigenetic modulators, of which the down-regulation of lysine acetyltransferase 2B [KAT2B] mRNA and protein was the most significant and was consequently validated in inflamed CD and UC compared with healthy colonic tissues. KAT2B protein localised abundantly in nuclei of normal colonic epithelium ...Continue Reading

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Citations

May 23, 2018·Inflammatory Bowel Diseases·Claire Liefferinckx, Denis Franchimont
Nov 9, 2018·Inflammatory Bowel Diseases·Greeshma Ray, Michelle S Longworth
Jun 26, 2020·Frontiers in Immunology·Zhonghua ZhengShiwei Duan
Feb 13, 2021·Critical Reviews in Microbiology·Shruti AhlawatKrishna Kant Sharma

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