Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
Ergebnis 23 von 47

Details

Autor(en) / Beteiligte
Titel
MTG16 regulates colonic epithelial differentiation, colitis, and tumorigenesis by repressing E protein transcription factors
Ist Teil von
  • JCI insight, 2022-05, Vol.7 (10)
Ort / Verlag
United States: American Society for Clinical Investigation
Erscheinungsjahr
2022
Quelle
MEDLINE
Beschreibungen/Notizen
  • Aberrant epithelial differentiation and regeneration contribute to colon pathologies, including inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). Myeloid translocation gene 16 (MTG16, also known as CBFA2T3) is a transcriptional corepressor expressed in the colonic epithelium. MTG16 deficiency in mice exacerbates colitis and increases tumor burden in CAC, though the underlying mechanisms remain unclear. Here, we identified MTG16 as a central mediator of epithelial differentiation, promoting goblet and restraining enteroendocrine cell development in homeostasis and enabling regeneration following dextran sulfate sodium-induced (DSS-induced) colitis. Transcriptomic analyses implicated increased Ephrussi box-binding transcription factor (E protein) activity in MTG16-deficient colon crypts. Using a mouse model with a point mutation that attenuates MTG16:E protein interactions (Mtg16P209T), we showed that MTG16 exerts control over colonic epithelial differentiation and regeneration by repressing E protein-mediated transcription. Mimicking murine colitis, MTG16 expression was increased in biopsies from patients with active IBD compared with unaffected controls. Finally, uncoupling MTG16:E protein interactions partially phenocopied the enhanced tumorigenicity of Mtg16-/- colon in the azoxymethane/DSS-induced model of CAC, indicating that MTG16 protects from tumorigenesis through additional mechanisms. Collectively, our results demonstrate that MTG16, via its repression of E protein targets, is a key regulator of cell fate decisions during colon homeostasis, colitis, and cancer.
Sprache
Englisch
Identifikatoren
ISSN: 2379-3708
eISSN: 2379-3708
DOI: 10.1172/jci.insight.153045
Titel-ID: cdi_doaj_primary_oai_doaj_org_article_5d314fb9ae044fb497de866e2b6326f8

Weiterführende Literatur

Empfehlungen zum selben Thema automatisch vorgeschlagen von bX