The mouse CCR2 gene is regulated by two promoters that are responsive to plasma cholesterol and peroxisome proliferator-activated receptor γ ligands

被引:29
作者
Chen, YM [1 ]
Green, SR [1 ]
Ho, J [1 ]
Li, A [1 ]
Almazan, F [1 ]
Quehenberger, O [1 ]
机构
[1] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA
关键词
CCR2; chemokines; promoter; gene expression; cholesterol; PPAR gamma; atherosclerosis;
D O I
10.1016/j.bbrc.2005.04.110
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:188 / 193
页数:6
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