Different regulation of the LXRalpha promoter activity by isoforms of CCAAT/enhancer-binding proteins.
LXRs have recently been shown to regulate key enzymes in cholesterol degradation, reverse transport of cholesterol from peripheral cells, cholesterol uptake and lipogenesis. The LXRalpha promoter was thus studied to investigate if LXRalpha gene expression is under the regulation of transcription factors involved in adipogenesis. We report that the C/EBP transcription factor interacts with the promoter of the LXRalpha gene. In in vitro footprinting experiments, protein extracts from several tissues gave footprints covering a putative C/EBP recognition site. Transfection experiments and EMSA showed a direct effect of these transcription factors on the LXRalpha promoter. C/EBPalpha upregulated expression of the reporter gene in an NIH 3T3-L1 preadipocyte cell line, while C/EBPbeta and C/EBPdelta had no effect. In liver hepatoma Fao II and Cos-7 kidney cells, both C/EBPalpha and C/EBPbeta downregulated expression of the reporter gene while C/EBPdelta induced activity, indicating that the functional consequences of C/EBP isoform interactions with the LXRalpha promoter are dependent on the cellular context. Monitoring of the LXR mRNA levels during adipose tissue differentiation showed that LXRbeta is constitutively expressed during the entire differentiation process while LXRalpha is induced upon addition of differentiation mix.
Steffensen
Knut R
KR
Department of Biosciences, Novum Research Park, Karolinska Institute, Huddinge S-14157, Sweden. knut.steffensen@biosci.ki.se
Schuster
Gertrud U
GU
Parini
Paolo
P
Holter
Elin
E
Sadek
Christine M
CM
Cassel
Tobias
T
Eskild
Winnie
W
Gustafsson
Jan-Ake
JA
D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D019556:COS Cells; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007930:Leucine / Q000737:chemistry; D000071518:Liver X Receptors; D051379:Mice; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000378:metabolism; D057093:Orphan Nuclear Receptors; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; D009841:Oligonucleotides; D057093:Orphan Nuclear Receptors; D020033:Protein Isoforms; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D002784:Cholesterol; D007930:Leucine