出版社：American Society for Biochemistry and Molecular Biology
摘要：In birds and mammals, agonists of the liver X receptor (LXR)increase the expression of enzymes that make up the fatty acidsynthesis pathway. Here, we investigate the mechanism by whichthe synthetic LXR agonist, T0-901317, increases the transcriptionof the acetyl-coenzyme A carboxylase- (ACC) gene in chick embryohepatocyte cultures. Transfection analyses demonstrate thatactivation of ACC transcription by T0-901317 is mediated bya cis-acting regulatory unit (–101 to –71 bp) thatis composed of a liver X receptor response element (LXRE) anda sterol-regulatory element (SRE). The SRE enhances the abilityof the LXRE to activate ACC transcription in the presence ofT0-901317. Treating hepatocytes with T0-901317 increases theconcentration of mature sterol-regulatory element binding protein-1(SREBP-1) in the nucleus and the acetylation of histone H3 andhistone H4 at the ACC LXR response unit. These results indicatethat T0-901317 increases hepatic ACC transcription by directlyactivating LXR•retinoid X receptor (RXR) heterodimers andby increasing the activity of an accessory transcription factor(SREBP-1) that enhances ligand induced-LXR•RXR activity.Supplementary key words fatty acid synthesis • sterol-regulatory element binding protein • thyroid hormone • chicken • histone acetylation
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