Previous Article | Next Article 
Molecular and Cellular Biology, November 2004, p. 9863-9872, Vol. 24, No. 22
0270-7306/04/$08.00+0 DOI: 10.1128/MCB.24.22.9863-9872.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
ETO/MTG8 Is an Inhibitor of C/EBPß Activity and a Regulator of Early Adipogenesis
Justin J. Rochford,
Robert K. Semple,
Matthias Laudes,
Keith B. Boyle,
Constantinos Christodoulides,
Claire Mulligan,
Christopher J. Lelliott,
Sven Schinner,
Dirk Hadaschik,
Meera Mahadevan,
Jaswinder K. Sethi,
Antonio Vidal-Puig, and
Stephen O'Rahilly*
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom
Received 28 January 2004/
Returned for modification 26 March 2004/
Accepted 30 July 2004
The putative transcriptional corepressor ETO/MTG8 has been extensively studied due to its involvement in a chromosomal translocation causing the t(8;21) form of acute myeloid leukemia. Despite this, the role of ETO in normal physiology has remained obscure. Here we show that ETO is highly expressed in preadipocytes and acts as an inhibitor of C/EBPß during early adipogenesis, contributing to its characteristically delayed activation. ETO prevents both the transcriptional activation of the C/EBP
promoter by C/EBPß and its concurrent accumulation in centromeric sites during early adipogenesis. ETO expression rapidly reduces after the initiation of adipogenesis, and this is essential to the normal induction of adipogenic gene expression. These findings define, for the first time, a molecular role for ETO in normal physiology as an inhibitor of C/EBPß and a novel regulator of early adipogenesis.
* Corresponding author. Mailing address: Department of Clinical Biochemistry, University of Cambridge, Box 232, Level 4, Addenbrooke's Hospital, Hills Rd., Cambridge CB2 2QR, United Kingdom. Phone: 44 (0) 1223-336855. Fax: 44 (0) 1223-330598. E-mail:
sorahill{at}hgmp.mrc.ac.uk.
Molecular and Cellular Biology, November 2004, p. 9863-9872, Vol. 24, No. 22
0022-538X/04/$08.00+0 DOI: 10.1128/MCB.24.22.9863-9872.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
This article has been cited by other articles:
-
Guo, C., Hu, Q., Yan, C., Zhang, J.
(2009). Multivalent Binding of the ETO Corepressor to E Proteins Facilitates Dual Repression Controls Targeting Chromatin and the Basal Transcription Machinery. Mol. Cell. Biol.
29: 2644-2657
[Abstract]
[Full Text]
-
Grimsey, N., Han, G.-S., O'Hara, L., Rochford, J. J., Carman, G. M., Siniossoglou, S.
(2008). Temporal and Spatial Regulation of the Phosphatidate Phosphatases Lipin 1 and 2. J. Biol. Chem.
283: 29166-29174
[Abstract]
[Full Text]
-
Chyla, B. J., Moreno-Miralles, I., Steapleton, M. A., Thompson, M. A., Bhaskara, S., Engel, M., Hiebert, S. W.
(2008). Deletion of Mtg16, a Target of t(16;21), Alters Hematopoietic Progenitor Cell Proliferation and Lineage Allocation. Mol. Cell. Biol.
28: 6234-6247
[Abstract]
[Full Text]
-
Payne, V. A., Grimsey, N., Tuthill, A., Virtue, S., Gray, S. L., Dalla Nora, E., Semple, R. K., O'Rahilly, S., Rochford, J. J.
(2008). The Human Lipodystrophy Gene BSCL2/Seipin May Be Essential for Normal Adipocyte Differentiation. Diabetes
57: 2055-2060
[Abstract]
[Full Text]
-
Kumar, R., Cheney, K. M., McKirdy, R., Neilsen, P. M., Schulz, R. B., Lee, J., Cohen, J., Booker, G. W., Callen, D. F.
(2008). CBFA2T3-ZNF652 Corepressor Complex Regulates Transcription of the E-box Gene HEB. J. Biol. Chem.
283: 19026-19038
[Abstract]
[Full Text]
-
Yokota, T., Bui, T., Liu, Y., Yi, M., Hunt, K. K., Keyomarsi, K.
(2007). Differential Regulation of Elafin in Normal and Tumor-Derived Mammary Epithelial Cells Is Mediated by CCAAT/Enhancer Binding Protein. Cancer Res.
67: 11272-11283
[Abstract]
[Full Text]
-
Gustafson, B., Hammarstedt, A., Andersson, C. X., Smith, U.
(2007). Inflamed Adipose Tissue: A Culprit Underlying the Metabolic Syndrome and Atherosclerosis. Arterioscler. Thromb. Vasc. Bio.
27: 2276-2283
[Abstract]
[Full Text]
-
Bezy, O., Vernochet, C., Gesta, S., Farmer, S. R., Kahn, C. R.
(2007). TRB3 Blocks Adipocyte Differentiation through the Inhibition of C/EBP{beta} Transcriptional Activity. Mol. Cell. Biol.
27: 6818-6831
[Abstract]
[Full Text]
-
Payne, V. A., Au, W.-S., Gray, S. L., Nora, E. D., Rahman, S. M., Sanders, R., Hadaschik, D., Friedman, J. E., O'Rahilly, S., Rochford, J. J.
(2007). Sequential Regulation of Diacylglycerol Acyltransferase 2 Expression by CAAT/Enhancer-binding Protein beta (C/EBPbeta) and C/EBP{alpha} during Adipogenesis. J. Biol. Chem.
282: 21005-21014
[Abstract]
[Full Text]
-
Sethi, J. K., Vidal-Puig, A. J.
(2007). Thematic review series: Adipocyte Biology. Adipose tissue function and plasticity orchestrate nutritional adaptation. J. Lipid Res.
48: 1253-1262
[Abstract]
[Full Text]
-
Kumar, R., Manning, J., Spendlove, H. E., Kremmidiotis, G., McKirdy, R., Lee, J., Millband, D. N., Cheney, K. M., Stampfer, M. R., Dwivedi, P. P., Morris, H. A., Callen, D. F.
(2006). ZNF652, A Novel Zinc Finger Protein, Interacts with the Putative Breast Tumor Suppressor CBFA2T3 to Repress Transcription. Mol Cancer Res
4: 655-665
[Abstract]
[Full Text]
-
Blumberg, J. M., Tzameli, I., Astapova, I., Lam, F. S., Flier, J. S., Hollenberg, A. N.
(2006). Complex Role of the Vitamin D Receptor and Its Ligand in Adipogenesis in 3T3-L1 Cells. J. Biol. Chem.
281: 11205-11213
[Abstract]
[Full Text]