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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{alpha} 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.



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