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ORIGINAL RESEARCH article
Front. Epigenet. Epigenom.
Sec. Epigenetics and Metabolism
Volume 2 - 2024 |
doi: 10.3389/freae.2024.1496999
This article is part of the Research Topic Epigenetic Basis of Circadian Rhythm and Metabolism View all articles
HDAC3 regulates the diurnal rhythms of claudin expression and intestinal permeability
Provisionally accepted- Carnegie Mellon University, Pittsburgh, United States
Circadian rhythms play an essential role in the regulation of intestinal absorption and barrier function.Tight junctions, including claudins, are fundamental components of the intestinal epithelial barrier.However, the regulatory mechanisms governing their diurnal expression remain poorly understood.Furthermore, the impact of circadian rhythms on intestinal permeability through claudin modulation has yet to be fully explored. Here we investigated the expression and the diurnal rhythms of claudin transcripts in the intestinal epithelium. We identified histone deacetylase 3 (HDAC3) as an epigenetic regulator that represses claudin expression and drives the diurnal rhythms via histone deacetylation.Loss of HDAC3 leads to increased intestinal permeability and dampened its diurnal rhythm. We further revealed that HDAC3 affects the basolateral localization of claudin-3. Together, our findings give insights into epigenetic modification in regulating tight junction and its diurnal rhythms, providing targets for therapeutic mediations in gastrointestinal disorders.
Keywords: histone deacetylation, claudin, Tight Junctions, HDAC3, circadian rhythms, intestinal permeability 2.2 RNA-sequencing (RNA-seq) data analysis
Received: 16 Sep 2024; Accepted: 11 Nov 2024.
Copyright: © 2024 Christopher, Zhang, Oladejo, Sharma and Kuang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Zheng Kuang, Carnegie Mellon University, Pittsburgh, United States
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