Deletion of Mtgr1 sensitizes the colonic epithelium to dextran sodium sulfate-induced colitis.

Background & Aims: The disruption of homeostasis between proliferation and apoptosis in the colonic epithelium contributes to the pathogenesis of human ulcerative colitis. Mice lacking the transcriptional corepressor myeloid translocation gene related-1 (Mtgr1) display impaired secretory cell lineage development in the small intestine and an increase in proliferation in the crypts of both the small and large intestines. Despite the increase in proliferating cells, the colons of Mtgr1-null mice have a normal cell lineage distribution and normal architecture.

Mtgr1 is a transcriptional corepressor that is required for maintenance of the secretory cell lineage in the small intestine.

Two members of the MTG/ETO family of transcriptional corepressors, MTG8 and MTG16, are disrupted by chromosomal translocations in up to 15% of acute myeloid leukemia cases. The third family member, MTGR1, was identified as a factor that associates with the t(8;21) fusion protein RUNX1-MTG8. We demonstrate that Mtgr1 associates with mSin3A, N-CoR, and histone deacetylase 3 and that when tethered to DNA, Mtgr1 represses transcription, suggesting that Mtgr1 also acts as a transcriptional corepressor.