PMID- 12048207 OWN - NLM STAT- MEDLINE DCOM- 20021024 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 277 IP - 38 DP - 2002 Sep 20 TI - Insulin and sterol-regulatory element-binding protein-1c (SREBP-1C) regulation of gene expression in 3T3-L1 adipocytes. Identification of CCAAT/enhancer-binding protein beta as an SREBP-1C target. PG - 35625-34 AB - We evaluated the hypothesis of sterol-regulatory element-binding protein (SREBP)-1c being a general mediator of the transcriptional effects of insulin, with a focus on adipocytes, in which insulin profoundly influences specific gene expression. Using real time quantitative reverse transcriptase-PCR to monitor changes in the expression of about 50 genes that cover a wide range of adipocyte functions, we have compared the impact of insulin treatment with that of adenoviral overexpression of either dominant positive or dominant negative SREBP-1c mutants in 3T3-L1 adipocytes. As expected, insulin up-regulated, dominant positive stimulated, and dominant negative decreased previously characterized direct SREBP targets (FAS, SCD-1, and low density lipoprotein receptor). We also identified three novel SREBP-1c transcriptional targets in adipocytes, which were confirmed by run-on assays: plasminogen activator inhibitor 1, CCAAT/enhancer-binding protein delta (C/EBPdelta), and C/EBPbeta. Because most insulin-regulated genes were also modulated by SREBP-1c mutants, our data establish that 1) SREBP-1c is an important mediator of insulin transcriptional effects in adipocytes, and 2) C/EBPbeta is under the direct control of SREBP-1c, as demonstrated by the ability of SREBP-1c to activate the transcription from C/EBPbeta promoter through canonical SREBP binding sites. Thus, some of the effects of insulin and/or SREBP-1c in mature fat cells might require C/EBPbeta or C/EBPdelta as transcriptional relays. FAU - Le Lay, Soazig AU - Le Lay S AD - INSERM Unite 465, Centre de Recherches Biomedicales des Cordeliers, 15 rue de l'Ecole de Medecine, 75270 Paris Cedex 06, France. FAU - Lefrere, Isabelle AU - Lefrere I FAU - Trautwein, Christian AU - Trautwein C FAU - Dugail, Isabelle AU - Dugail I FAU - Krief, Stephane AU - Krief S LA - eng PT - Journal Article DEP - 20020604 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (CCAAT-Enhancer-Binding Protein-beta) RN - 0 (CCAAT-Enhancer-Binding Proteins) RN - 0 (DNA Primers) RN - 0 (DNA-Binding Proteins) RN - 0 (Insulin) RN - 0 (Srebf1 protein, mouse) RN - 0 (Sterol Regulatory Element Binding Protein 1) RN - 0 (Transcription Factors) SB - IM MH - 3T3 Cells MH - Adipocytes/*metabolism MH - Animals MH - Base Sequence MH - CCAAT-Enhancer-Binding Protein-beta/*metabolism MH - CCAAT-Enhancer-Binding Proteins/metabolism/*physiology MH - DNA Primers MH - DNA-Binding Proteins/metabolism/*physiology MH - Gene Expression Regulation/*physiology MH - Insulin/*physiology MH - Mice MH - Sterol Regulatory Element Binding Protein 1 MH - *Transcription Factors MH - Transcription, Genetic/physiology EDAT- 2002/06/06 10:00 MHDA- 2002/10/31 04:00 CRDT- 2002/06/06 10:00 PHST- 2002/06/06 10:00 [pubmed] PHST- 2002/10/31 04:00 [medline] PHST- 2002/06/06 10:00 [entrez] AID - S0021-9258(18)36803-0 [pii] AID - 10.1074/jbc.M203913200 [doi] PST - ppublish SO - J Biol Chem. 2002 Sep 20;277(38):35625-34. doi: 10.1074/jbc.M203913200. Epub 2002 Jun 4.