| Autor: |
Hannah M. Kolev, Avital Swisa, Elisabetta Manduchi, Yemin Lan, Rachel R. Stine, Giuseppe Testa, Klaus H. Kaestner |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Cellular and Molecular Gastroenterology and Hepatology, Vol 15, Iss 4, Pp 821-839 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2352-345X |
| DOI: |
10.1016/j.jcmgh.2022.12.001 |
| Popis: |
Background & Aims: Although trimethylation of histone H3 lysine 27 (H3K27me3) by polycomb repressive complex 2 is required for intestinal function, the role of the antagonistic process—H3K27me3 demethylation—in the intestine remains unknown. The aim of this study was to determine the contribution of H3K27me3 demethylases to intestinal homeostasis. Methods: An inducible mouse model was used to simultaneously ablate the 2 known H3K27me3 demethylases, lysine (K)-specific demethylase 6A (Kdm6a) and lysine (K)-specific demethylase 6B (Kdm6b), from the intestinal epithelium. Mice were analyzed at acute and prolonged time points after Kdm6a/b ablation. Cellular proliferation and differentiation were measured using immunohistochemistry, while RNA sequencing and chromatin immunoprecipitation followed by sequencing for H3K27me3 were used to identify gene expression and chromatin changes after Kdm6a/b loss. Intestinal epithelial renewal was evaluated using a radiation-induced injury model, while Paneth cell homeostasis was measured via immunohistochemistry, immunoblot, and transmission electron microscopy. Results: We did not detect any effect of Kdm6a/b ablation on intestinal cell proliferation or differentiation toward the secretory cell lineages. Acute and prolonged Kdm6a/b loss perturbed expression of gene signatures belonging to multiple cell lineages (adjusted P value < .05), and a set of 72 genes was identified as being down-regulated with an associated increase in H3K27me3 levels after Kdm6a/b ablation (false discovery rate, |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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