The abundance of H3K27me3 histone modification in the mouse colon under chronic inflammation

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Abstract

The prevalence of inflammatory bowel diseases (IBD) has increased globally over recent decades. Following industrialization, the incidence of IBD has been rising not only in European and North American countries but also in Asian nations, including China and India. Despite its widespread occurrence and extensive research efforts, the etiopathogenesis of IBD remains incompletely understood. Epigenetic mechanisms, such as DNA methylation and post-translational modifications of histones, play a crucial role in its pathogenesis. Histone modifications influence chromatin structure and can serve as markers for transcriptionally active or inactive regions. Given the global alterations in gene expression profiles observed in the intestines of IBD patients, it is plausible to hypothesize comprehensive structural changes in chromatin activity and accessibility during intestinal inflammatory processes, affecting both mucosal immune cells and epithelial cells. Particularly, studies utilizing colonic tissue samples from patients with enterocolitis have demonstrated a reduction in the overall levels of trimethylation of histone H3 at lysine 27 (H3K27me3) within epithelial cells. Concurrently, targeting the H3K27me3 modification presents a promising therapeutic approach for IBD through the regulation of transcription in immune cells. This research investigated the presence of this histone modification in epithelial cell nuclei and in colonic tissue as a whole within two mouse models of chronic colitis. Our findings indicate that the overall level of H3K27me3 increases in the nuclei of enterocytes in a chronic colitis model with Muc2 gene knockout. This result suggests that the H3K27me3 modification significantly influences the pathogenesis of IBD, not only in immune cells but also in colonic epithelial cells.

About the authors

E. A. Nickelvart

Institute of Molecular and Cellular Biology, Siberian Branch of the Russian Academy of Sciences

Novosibirsk, Russia

S. S. Medvedeva

Institute of Molecular and Cellular Biology, Siberian Branch of the Russian Academy of Sciences

Novosibirsk, Russia

J. V. Popova

Institute of Molecular and Cellular Biology, Siberian Branch of the Russian Academy of Sciences

Novosibirsk, Russia

E. N. Kozhevnikova

Institute of Molecular and Cellular Biology, Siberian Branch of the Russian Academy of Sciences

Email: kozhevnikova@mcb.nsc.ru
Novosibirsk, Russia

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