Sequential regulation of diacylglycerol acyltransferase 2 expression by CAAT/enhancer-binding protein beta (C/EBPbeta) and C/EBPalpha during adipogenesis.
Diacylglycerol acyltransferase 2 (DGAT2) catalyzes the final step of triacylglycerol (TG) synthesis. Despite the existence of an alternative acyltransferase (DGAT1), mice lacking DGAT2 have a severe deficiency of TG in adipose tissue, indicating a nonredundant role for this enzyme in adipocyte TG synthesis. We have studied the regulation of DGAT2 expression during adipogenesis. In both isolated murine preadipocytes and 3T3-L1 cells the temporal pattern of DGAT2 expression closely mimicked that of genes whose expression is regulated by CAAT/enhancer-binding protein beta (C/EBPbeta). Inhibition of C/EBPbeta expression in differentiating preadipocytes reduced DGAT2 expression, and electrophoretic mobility shift assay and chromatin immunoprecipitation experiments identified a promoter element in the DGAT2 gene that is likely to mediate this effect. The importance of C/EBPbeta in adipocyte expression of DGAT2 was confirmed by the finding of reduced DGAT2 expression in the adipose tissue of C/EBPbeta-null animals. However, DGAT2 expression is maintained at high levels during the later stages of adipogenesis, when C/EBPbeta levels decline. We show that, at these later stages of differentiation, C/EBPalpha is capable of substituting for C/EBPbeta at the same promoter element. These observations provide novel insight into the transcriptional regulation of DGAT2 expression. Moreover, they further refine the complex and serial roles of the C/EBP family of transcription factors in inducing and maintaining the metabolic properties of mature adipocytes.
Payne
Victoria A
VA
Department of Clinical Biochemistry, University of Cambridge, Box 232, Level 4, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QR, United Kingdom.
Au
Wo-Shing
WS
Gray
Sarah L
SL
Nora
Edoardo Dalla
ED
Rahman
Shaikh M
SM
Sanders
Rebecca
R
Hadaschik
Dirk
D
Friedman
Jacob E
JE
O'rahilly
Stephen
S
Rochford
Justin J
JJ
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D002454:Cell Differentiation; D051048:Diacylglycerol O-Acyltransferase / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D051379:Mice; D008954:Models, Biological; D011401:Promoter Regions, Genetic; D012313:RNA / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism
D022763:CCAAT-Enhancer-Binding Protein-alpha; D022782:CCAAT-Enhancer-Binding Protein-beta; D034741:RNA, Small Interfering; D012313:RNA; C516957:DGAT2 protein, mouse; D051048:Diacylglycerol O-Acyltransferase