ETO/MTG8 is an inhibitor of C/EBPbeta activity and a regulator of early adipogenesis.
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/EBPbeta during early adipogenesis, contributing to its characteristically delayed activation. ETO prevents both the transcriptional activation of the C/EBPalpha promoter by C/EBPbeta 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/EBPbeta and a novel regulator of early adipogenesis.
Rochford
Justin J
JJ
Department of Clinical Biochemistry, University of Cambridge, Box 232, Level 4, Addenbrooke's Hospital, Hills Rd., Cambridge CB2 2QR, United Kingdom.
Semple
Robert K
RK
Laudes
Matthias
M
Boyle
Keith B
KB
Christodoulides
Constantinos
C
Mulligan
Claire
C
Lelliott
Christopher J
CJ
Schinner
Sven
S
Hadaschik
Dirk
D
Mahadevan
Meera
M
Sethi
Jaswinder K
JK
Vidal-Puig
Antonio
A
O'Rahilly
Stephen
S
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000254:growth & development* / Q000378:metabolism*; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000037:antagonists & inhibitors*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D050356:Lipid Metabolism; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D000075142:RUNX1 Translocation Partner 1 Protein; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D022782:CCAAT-Enhancer-Binding Protein-beta; D004268:DNA-Binding Proteins; C493598:MTG8 protein, mouse; D011518:Proto-Oncogene Proteins; D000075142:RUNX1 Translocation Partner 1 Protein; C082222:RUNX1T1 protein, human; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors