The mouse CCR2 gene is regulated by two promoters that are responsive to plasma cholesterol and peroxisome proliferator-activated receptor gamma ligands.
We have previously shown that the expression of monocyte CCR2, the receptor for monocyte chemoattractant protein-1, is induced by plasma cholesterol. The present study examines the mechanisms that regulate monocyte CCR2 expression in hypercholesterolemia using a mouse model. Our data demonstrate that in the mouse, CCR2 expression in circulating monocytes is controlled by two promoters P1 and P2. The two distinct transcripts, which encode the same protein, are produced by alternative splicing in the 5'-untranslated region. Both promoters are constitutively active, but only P2 is stimulated by cholesterol. However, both promoters are repressed by peroxisome proliferator-activated receptor gamma.
Chen
Yiming
Y
Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0682, USA.
Green
Simone R
SR
Ho
Jessica
J
Li
Andrew
A
Almazan
Felizidad
F
Quehenberger
Oswald
O
D000818:Animals; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood*; D005786:Gene Expression Regulation / Q000187:drug effects; D006937:Hypercholesterolemia / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
C515335:Ccr2 protein, mouse; D047495:PPAR gamma; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D002784:Cholesterol