Intestinal regulation of suppression of tumorigenicity 14 (ST14) and serine peptidase inhibitor, Kunitz type -1 (SPINT1) by transcription factor CDX2.

Erik Thomas Danielsen, Anders Krüger Olsen, Mehmet Coskun, Annika W. Nonboe, Sylvester Larsen, Katja Dahlgaard, Eric Paul Bennett, Cathy Mitchelmore, Lotte Katrine Vogel, Jesper Troelsen

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Resumé

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.
OriginalsprogEngelsk
Artikelnummer11813
TidsskriftScientific Reports
Vol/bind8
Udgave nummer1
ISSN2045-2322
DOI
StatusUdgivet - 7 aug. 2018

Citer dette

Danielsen, Erik Thomas ; Olsen, Anders Krüger ; Coskun, Mehmet ; Nonboe, Annika W. ; Larsen, Sylvester ; Dahlgaard, Katja ; Bennett, Eric Paul ; Mitchelmore, Cathy ; Vogel, Lotte Katrine ; Troelsen, Jesper. / Intestinal regulation of suppression of tumorigenicity 14 (ST14) and serine peptidase inhibitor, Kunitz type -1 (SPINT1) by transcription factor CDX2. I: Scientific Reports. 2018 ; Bind 8, Nr. 1.
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abstract = "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.",
author = "Danielsen, {Erik Thomas} and Olsen, {Anders Kr{\"u}ger} and Mehmet Coskun and Nonboe, {Annika W.} and Sylvester Larsen and Katja Dahlgaard and Bennett, {Eric Paul} and Cathy Mitchelmore and Vogel, {Lotte Katrine} and Jesper Troelsen",
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Intestinal regulation of suppression of tumorigenicity 14 (ST14) and serine peptidase inhibitor, Kunitz type -1 (SPINT1) by transcription factor CDX2. / Danielsen, Erik Thomas; Olsen, Anders Krüger; Coskun, Mehmet; Nonboe, Annika W.; Larsen, Sylvester; Dahlgaard, Katja; Bennett, Eric Paul; Mitchelmore, Cathy; Vogel, Lotte Katrine; Troelsen, Jesper.

I: Scientific Reports, Bind 8, Nr. 1, 11813, 07.08.2018.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Intestinal regulation of suppression of tumorigenicity 14 (ST14) and serine peptidase inhibitor, Kunitz type -1 (SPINT1) by transcription factor CDX2.

AU - Danielsen, Erik Thomas

AU - Olsen, Anders Krüger

AU - Coskun, Mehmet

AU - Nonboe, Annika W.

AU - Larsen, Sylvester

AU - Dahlgaard, Katja

AU - Bennett, Eric Paul

AU - Mitchelmore, Cathy

AU - Vogel, Lotte Katrine

AU - Troelsen, Jesper

PY - 2018/8/7

Y1 - 2018/8/7

N2 - 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.

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JO - Scientific Reports

JF - Scientific Reports

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