Genomic analysis of 1,25-dihydroxyvitamin D 3 action in mouse intestine reveals compartment and segment-specific gene regulatory effects.

Autor:	Aita R; Department of Genetics, Human Genetics Institute of New Jersey, Rutgers Cancer Institute of New Jersey, Institute of Food, Nutrition, and Health, EOHSI, Rutgers University, New Jersey, USA., Aldea D; Department of Genetics, Human Genetics Institute of New Jersey, Rutgers Cancer Institute of New Jersey, Institute of Food, Nutrition, and Health, EOHSI, Rutgers University, New Jersey, USA., Hassan S; Department of Genetics, Human Genetics Institute of New Jersey, Rutgers Cancer Institute of New Jersey, Institute of Food, Nutrition, and Health, EOHSI, Rutgers University, New Jersey, USA., Hur J; Department of Genetics, Human Genetics Institute of New Jersey, Rutgers Cancer Institute of New Jersey, Institute of Food, Nutrition, and Health, EOHSI, Rutgers University, New Jersey, USA., Pellon-Cardenas O; Department of Genetics, Human Genetics Institute of New Jersey, Rutgers Cancer Institute of New Jersey, Institute of Food, Nutrition, and Health, EOHSI, Rutgers University, New Jersey, USA., Cohen E; Department of Genetics, Human Genetics Institute of New Jersey, Rutgers Cancer Institute of New Jersey, Institute of Food, Nutrition, and Health, EOHSI, Rutgers University, New Jersey, USA., Chen L; Department of Genetics, Human Genetics Institute of New Jersey, Rutgers Cancer Institute of New Jersey, Institute of Food, Nutrition, and Health, EOHSI, Rutgers University, New Jersey, USA., Shroyer N; Department of Medicine, Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA., Christakos S; Department of Microbiology, Biochemistry, and Molecular Genetics, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, New Jersey, USA. Electronic address: christak@njms.rutgers.edu., Verzi MP; Department of Genetics, Human Genetics Institute of New Jersey, Rutgers Cancer Institute of New Jersey, Institute of Food, Nutrition, and Health, EOHSI, Rutgers University, New Jersey, USA. Electronic address: Verzi@biology.rutgers.edu., Fleet JC; Department of Nutritional Science, University of Texas, Austin, Texas, USA. Electronic address: james.fleet@austin.utexas.edu.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2022 Aug; Vol. 298 (8), pp. 102213. Date of Electronic Publication: 2022 Jun 30.
DOI:	10.1016/j.jbc.2022.102213
Abstrakt:	1,25-dihydroxyvitamin D (VD) regulates intestinal calcium absorption in the small intestine (SI) and also reduces risk of colonic inflammation and cancer. However, the intestine compartment-specific target genes of VD signaling are unknown. Here, we examined VD action across three functional compartments of the intestine using RNA-seq to measure VD-induced changes in gene expression and Chromatin Immunoprecipitation with next generation sequencing to measure vitamin D receptor (VDR) genomic binding. We found that VD regulated the expression of 55 shared transcripts in the SI crypt, SI villi, and in the colon, including Cyp24a1, S100g, Trpv6, and Slc30a10. Other VD-regulated transcripts were unique to the SI crypt (162 up, 210 down), villi (199 up, 63 down), or colon (102 up, 28 down), but this did not correlate with mRNA levels of the VDR. Furthermore, bioinformatic analysis identified unique VD-regulated biological functions in each compartment. VDR-binding sites were found in 70% of upregulated genes from the colon and SI villi but were less common in upregulated genes from the SI crypt and among downregulated genes, suggesting some transcript-level VD effects are likely indirect. Consistent with this, we show that VD regulated the expression of other transcription factors and their downstream targets. Finally, we demonstrate that compartment-specific VD-mediated gene expression was associated with compartment-specific VDR-binding sites (<30% of targets) and enrichment of intestinal transcription factor-binding motifs within VDR-binding peaks. Taken together, our data reveal unique spatial patterns of VD action in the intestine and suggest novel mechanisms that could account for compartment-specific functions of this hormone. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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