Opposite regulation of the human apolipoprotein M gene by hepatocyte nuclear factor 1 and Jun transcription factors.
J Biol Chem
; 286(19): 17259-69, 2011 May 13.
Article
in En
| MEDLINE
| ID: mdl-21454713
ABSTRACT
HDL is a negative risk factor for atherosclerosis because of its multiple atheroprotective functions. Inflammation converts HDL particles from anti-atherogenic to pro-atherogenic, and this transformation is associated with changes in HDL structure and composition. Apolipoprotein M (apoM) has been recently shown to play a role in the maturation of HDL in plasma and to protect from atherosclerosis. ApoM gene is expressed primarily in the liver and kidney and is down-regulated by pro-inflammatory signals. We now show that the human apoM promoter harbors a dual specificity regulatory element in the proximal region that binds hepatocyte nuclear factor 1 (HNF-1) and members of the AP-1 family of pro-inflammatory transcription factors (c-Jun and JunB). Overexpression of c-Jun or JunB repressed both the basal and the HNF-1-mediated transactivation of the human apoM promoter. Treatment of HepG2 cells with potent inflammation-inducing phorbol esters or overexpression of PKCα was associated with a marked inhibition of apoM gene expression in a c-Jun/JunB-dependent manner. We provide evidence for a novel mechanism of inflammation-induced transcriptional repression that is based on the competition between HNF-1 and Jun proteins for binding to the same regulatory region. A similar mechanism accounts for the down-regulation of the liver-specific apolipoprotein A-II gene by Jun factors. Our studies provide novel insights on the mechanisms that control the expression of liver-specific apolipoprotein genes during inflammation and could affect the maturation and the functionality of HDL particles.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Apolipoproteins
/
Gene Expression Regulation
/
Proto-Oncogene Proteins c-jun
/
Hepatocyte Nuclear Factor 1
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
J Biol Chem
Year:
2011
Type:
Article
Affiliation country:
Greece