期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 25, 期 21, 页码 9576-9585出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.25.21.9576-9585.2005
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资金
- NCI NIH HHS [R01 CA064140, T32 CA009582, R01 CA077274, R01 CA112005, R01 CA 64140, P30 CA068485, CA 68485, R01 CA 77274, R01 CA 87549, CA 46413, R01 CA087549, R01 CA046413, T32 CA 09582, R01 CA 112005] Funding Source: Medline
- NIDDK NIH HHS [P30 DK058404, T32 DK 07673, T32 DK007673, 5P30 DK 58404-03] Funding Source: Medline
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. To define the biological function of Mtgr1, we created Mtgr1-null mice. These mice are proportionally smaller than their littermates during embryogenesis and throughout their life span but otherwise develop normally. However, these mice display a progressive reduction in the secretory epithelial cell lineage in the small intestine. This is not due to the loss of small intestinal progenitor cells expressing Gfi1, which is required for the formation of goblet and Paneth cells, implying that loss of Mtgr1 impairs the maturation of secretory cells in the small intestine.
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