{"doi":"10.1172/jci.insight.153045","title":"MTG16 regulates colonic epithelial differentiation, colitis, and tumorigenesis by repressing E protein transcription factors","abstract":"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.","journal":"JCI Insight","year":2022,"id":269242,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9468,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":818980,"name":"Justin Jacobse","orcid":"0000-0002-1899-0319","position":1,"is_corresponding":false},{"id":818981,"name":"Shruti A. 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Choksi","orcid":"0000-0003-1717-4472","position":11,"is_corresponding":false},{"id":51083,"name":"Kimmo Palin","orcid":"0000-0002-4621-6128","position":12,"is_corresponding":false},{"id":263090,"name":"M. Blanca Piazuelo","orcid":"0000-0002-0000-1324","position":13,"is_corresponding":false},{"id":86848,"name":"M. Kay Washington","orcid":"0000-0002-9589-7695","position":14,"is_corresponding":false},{"id":60556,"name":"Ken S. Lau","orcid":"0000-0001-8438-0319","position":15,"is_corresponding":false},{"id":86846,"name":"Jeremy A. Goettel","orcid":"0000-0002-0749-2357","position":16,"is_corresponding":false},{"id":333583,"name":"Scott W. Hiebert","orcid":"0000-0001-5621-1454","position":17,"is_corresponding":false},{"id":291497,"name":"Sarah P. Short","orcid":"0000-0001-9606-7370","position":18,"is_corresponding":false},{"id":291506,"name":"Christopher S. Williams","orcid":"0000-0002-1541-579X","position":19,"is_corresponding":false},{"id":512458,"name":"Rachel E. 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