CDX2 regulates interleukin‐33 gene expression in intestinal epithelial cells (LS174T)
| Autor: | Claus Henrik Nielsen, Jakob Benedict Seidelin, Mehmet Coşkun, Sylvester Larsen, Ole Birger Pedersen, Eric P. Bennett, Jesper T. Troelsen, Johanne Davidsen, Katja Dahlgaard |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
QH301-705.5 Biology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences interleukin‐33 0302 clinical medicine inflammatory bowel disease intestinal regulation Gene expression Tumor Cells Cultured Transcriptional regulation Humans CDX2 Transcription Factor RNA Messenger Biology (General) CDX2 Enhancer Transcription factor Gene Research Articles Regulation of gene expression Caudal‐related homeobox transcription factor 2 Epithelial Cells Interleukin-33 digestive system diseases Cell biology Intestines Interleukin 33 030104 developmental biology 030220 oncology & carcinogenesis embryonic structures gene regulation Research Article transcriptional control |
| Zdroj: | FEBS Open Bio, Vol 11, Iss 6, Pp 1638-1644 (2021) FEBS Open Bio Larsen, S, Seidelin, J B, Davidsen, J, Dahlgaard, K, Nielsen, C H, Bennett, E P, Pedersen, O B, Coskun, M & Troelsen, J T 2021, ' CDX2 regulates interleukin-33 gene expression in intestinal epithelial cells (LS174T) ', FEBS Open Bio, vol. 11, no. 6, pp. 1638-1644 . https://doi.org/10.1002/2211-5463.13161 |
| ISSN: | 2211-5463 |
| DOI: | 10.1002/2211-5463.13161 |
| Popis: | Dysregulation of interleukin‐33 (IL‐33) has been implicated in the pathogenesis of several autoimmune and inflammatory diseases, but few studies have examined transcriptional regulation of the IL33 gene. In the intestines, gene regulation is controlled by a transcription factor network of which the intestinal‐specific transcription factor CDX2 is a key component. In this study, we investigated whether CDX2 regulates IL33 mRNA expression. We examined IL33 mRNA expression in primary colonic epithelial cells from healthy humans and epithelial cell lines, revealing high expression levels in primary colonic and LS174T cells. Combining genomics data (ChIP‐seq, RNA‐seq) and IL33 promoter analyses in LS174T cells revealed intronic enhancer activity in the IL33 gene that is dependent on CDX2 expression. Western blotting and qRT‐PCR confirmed that IL33 expression is upregulated in a CDX2 concentration‐dependent manner, thereby providing the first evidence that CDX2 regulates the expression of IL33. We investigated whether the intestinal‐specific master transcription factor CDX2 regulates IL33 mRNA expression in intestinal epithelial cells, revealing high expression levels in primary colonic and LS174T cells. Combining ChIP‐Seq, RNA‐Seq, IL33 promoter analyses, western blotting, and qRT‐PCR revealed both a CDX2‐dependent enhancer and a CDX2 concentration‐dependent upregulation of IL33 expression, providing the first evidence of CDX2 regulating IL33 expression. |
| Databáze: | OpenAIRE |
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