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Molecular and Cellular Biology, November 2005, p. 9576-9585, Vol. 25, No. 21
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.21.9576-9585.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Mtgr1 Is a Transcriptional Corepressor That Is Required for Maintenance of the Secretory Cell Lineage in the Small Intestine

Joseph M. Amann,¹ Brenda J. Irvin Chyla,¹ Tiffany C. Ellis,¹ Andres Martinez,² Amy C. Moore,¹ Jeffrey L. Franklin,^3,4 Laura McGhee,⁵ Shari Meyers,⁵ Joyce E. Ohm,⁶ K. Scott Luce,¹ Andre J. Ouelette,⁷ M. Kay Washington,^4,8 Mary Ann Thompson,^4,8 Dana King,¹ Shiva Gautam,^4,9 Robert J. Coffey,^4,10,11 Robert H. Whitehead,^4,10 and Scott W. Hiebert^1,4*

Department of Biochemistry,¹ Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology & Nutrition,² Cell and Developmental Biology,³ Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232,⁴ Department of Biochemistry and Molecular Biology F7-26, Louisiana State University Health Sciences Center and Feist-Weiller Cancer Center, 1501 Kings Highway, Shreveport, Louisiana 71130,⁵ Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232,⁶ Department of Pathology, University of California, Irvine, D440 Medical Sciences I, Irvine, California 92697-4800,⁷ Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232,⁸ Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232,⁹ Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232,¹⁰ Department of Veterans Affairs Medical Center, Nashville, Tennessee 37232,¹¹

Received 17 March 2005/ Returned for modification 5 May 2005/ Accepted 7 August 2005

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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* Corresponding author. Mailing address: Department of Biochemistry, 512 Preston Research Building, Vanderbilt University School of Medicine, 23rd and Pierce Ave., Nashville TN 37232. Phone: (615) 936-3582. Fax: (615) 936-1790. E-mail: scott.hiebert{at}vanderbilt.edu.

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Molecular and Cellular Biology, November 2005, p. 9576-9585, Vol. 25, No. 21
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.21.9576-9585.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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