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. 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.
Amann
Joseph M
JM
Department of Biochemistry, 512 Preston Research Building, Vanderbilt University School of Medicine, 23rd and Pierce Avenue, Nashville, TN 37232, USA.
Chyla
Brenda J Irvin
BJ
Ellis
Tiffany C
TC
Martinez
Andres
A
Moore
Amy C
AC
Franklin
Jeffrey L
JL
McGhee
Laura
L
Meyers
Shari
S
Ohm
Joyce E
JE
Luce
K Scott
KS
Ouelette
Andre J
AJ
Washington
M Kay
MK
Thompson
Mary Ann
MA
King
Dana
D
Gautam
Shiva
S
Coffey
Robert J
RJ
Whitehead
Robert H
RH
Hiebert
Scott W
SW
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
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