title: Mtgr1 is a transcriptional corepressor that is required for maintenance of the secretory cell lineage in the small intestine.
abstract: 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.
authors.affiliation: Department of Biochemistry, 512 Preston Research Building, Vanderbilt University School of Medicine, 23rd and Pierce Avenue, Nashville, TN 37232, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Amann
authors.forename: Brenda J Irvin
authors.initials: BJ
authors.lastname: Chyla
authors.forename: Tiffany C
authors.initials: TC
authors.lastname: Ellis
authors.forename: Andres
authors.initials: A
authors.lastname: Martinez
authors.forename: Amy C
authors.initials: AC
authors.lastname: Moore
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Franklin
authors.forename: Laura
authors.initials: L
authors.lastname: McGhee
authors.forename: Shari
authors.initials: S
authors.lastname: Meyers
authors.forename: Joyce E
authors.initials: JE
authors.lastname: Ohm
authors.forename: K Scott
authors.initials: KS
authors.lastname: Luce
authors.forename: Andre J
authors.initials: AJ
authors.lastname: Ouelette
authors.forename: M Kay
authors.initials: MK
authors.lastname: Washington
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Thompson
authors.forename: Dana
authors.initials: D
authors.lastname: King
authors.forename: Shiva
authors.initials: S
authors.lastname: Gautam
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Coffey
authors.forename: Robert H
authors.initials: RH
authors.lastname: Whitehead
authors.forename: Scott W
authors.initials: SW
authors.lastname: Hiebert
mesh_terms: D000818:Animals; D002460:Cell Line; D019070:Cell Lineage / Q000502:physiology*; D002522:Chlorocebus aethiops; D019858:Enteroendocrine Cells / Q000166:cytology; D020397:Goblet Cells / Q000166:cytology; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D007421:Intestine, Small / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D056971:Nuclear Receptor Co-Repressor 1; D019879:Paneth Cells / Q000166:cytology; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000235:genetics; D011485:Protein Binding; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014158:Transcription, Genetic; D000099186:Histone Deacetylase 3
chemical_list: D006655:Histone Deacetylases; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D010750:Phosphoproteins; D012097:Repressor Proteins; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D000099186:Histone Deacetylase 3; C110408:CBFA2T2 myeloid-transforming gene-related protein; C539127:NCOR1 protein, human; C539128:Ncor1 protein, mouse; C099683:SIN3A transcription factor