Intestinal regulation of suppression of tumorigenicity 14 (ST14) and serine peptidase inhibitor, Kunitz type -1 (SPINT1) by transcription factor CDX2
| Autor: | Eric P. Bennett, Lotte K. Vogel, Jesper T. Troelsen, Mehmet Coşkun, E. Thomas Danielsen, Cathy Mitchelmore, Anders Krüger Olsen, Annika W. Nonboe, Katja Dahlgaard, Sylvester Larsen |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
SPINT1 Gene lcsh:Medicine Cell Cycle Proteins ST14 Article 03 medical and health sciences Gene expression Humans CDX2 Transcription Factor Matriptase Intestinal Mucosa lcsh:Science CDX2 Transcription factor Regulation of gene expression Multidisciplinary biology lcsh:R Serine Endopeptidases Promoter Phosphoproteins digestive system diseases Cell biology Enhancer Elements Genetic 030104 developmental biology Gene Expression Regulation embryonic structures biology.protein lcsh:Q Caco-2 Cells Microtubule-Associated Proteins HeLa Cells |
| Zdroj: | Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-14 (2018) Danielsen, E T, Olsen, A K, Coskun, M, Nonboe, A W, Larsen, S, Dahlgaard, K, Bennett, E P, Mitchelmore, C, Vogel, L K & Troelsen, J T 2018, ' Intestinal regulation of suppression of tumorigenicity 14 (ST14) and serine peptidase inhibitor, Kunitz type-1 (SPINT1) by transcription factor CDX2 ', Scientific Reports, vol. 8, 11813, pp. 1-14 . https://doi.org/10.1038/s41598-018-30216-z |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-018-30216-z |
| Popis: | The type II membrane-anchored serine protease, matriptase, encoded by suppression of tumorgenicity-14 (ST14) regulates the integrity of the intestinal epithelial barrier in concert with its inhibitor, HAI-1 encoded by serine peptidase inhibitor, Kunitz type -1 (SPINT1). The balance of the protease/inhibitor gene expression ratio is vital in preventing the oncogenic potential of matriptase. The intestinal cell lineage is regulated by a transcriptional regulatory network where the tumor suppressor, Caudal homeobox 2 (CDX2) is considered to be an intestinal master transcription factor. In this study, we show that CDX2 has a dual function in regulating both ST14 and SPINT1, gene expression in intestinal cells. We find that CDX2 is not required for the basal ST14 and SPINT1 gene expression; however changes in CDX2 expression affects the ST14/SPINT1 mRNA ratio. Exploring CDX2 ChIP-seq data from intestinal cell lines, we identified genomic CDX2-enriched enhancer elements for both ST14 and SPINT1, which regulate their corresponding gene promoter activity. We show that CDX2 displays both repressive and enhancing regulatory abilities in a cell specific manner. Together, these data reveal new insight into transcriptional mechanisms controlling the intestinal matriptase/inhibitor balance. |
| Databáze: | OpenAIRE |
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