PMID- 16024918 OWN - NLM STAT- MEDLINE DCOM- 20060112 LR - 20220227 IS - 0022-2275 (Print) IS - 0022-2275 (Linking) VI - 46 IP - 10 DP - 2005 Oct TI - The human ABCG1 gene: identification of LXR response elements that modulate expression in macrophages and liver. PG - 2151-67 AB - The ABC transporter ABCG1 (ATP binding cassette transporter G1), expressed in macrophages, liver, and other tissues, has been implicated in the efflux of cholesterol to high density lipoprotein. The ABCG1 gene is transcriptionally activated by cholesterol loading and activators of liver X receptors (LXRs) and retinoid X receptors (RXRs) through genomic sequences that have not been fully characterized. Here we show that ABCG1 mRNA is induced by LXR agonists in RAW264.7 macrophage cells, HepG2 hepatoma cells, and primary mouse hepatocytes. We identify two evolutionarily highly conserved LXR response elements (LXREs), LXRE-A and LXRE-B, located in the first and second introns of the human ABCG1 gene. Each element conferred robust LXR-agonist responsiveness to ABCG1 promoter-directed luciferase gene constructs in RAW264.7 and HepG2 cells. Overexpression of LXR/RXR activated the ABCG1 promoter in the presence of LXRE-A or LXRE-B sequences. In gel-shift assays, LXR/RXR heterodimers bound to wild-type but not to mutated LXRE-A and LXRE-B sequences. In chromatin immunoprecipitation assays, LXR and RXR were detected at LXRE-A and -B regions of DNA of human THP-1 macrophages. These studies clarify the mechanism of transcriptional upregulation of the ABCG1 gene by oxysterols in macrophages and liver, two key tissues where ABCG1 expression may affect cholesterol balance and atherogenesis. FAU - Sabol, Steven L AU - Sabol SL AD - Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. slsabol@mail.nih.gov FAU - Brewer, H Bryan Jr AU - Brewer HB Jr FAU - Santamarina-Fojo, Silvia AU - Santamarina-Fojo S LA - eng GR - Intramural NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, N.I.H., Intramural PT - Research Support, U.S. Gov't, P.H.S. DEP - 20050716 PL - United States TA - J Lipid Res JT - Journal of lipid research JID - 0376606 RN - 0 (ABCG1 protein, human) RN - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1) RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (DNA-Binding Proteins) RN - 0 (Hydrocarbons, Fluorinated) RN - 0 (Liver X Receptors) RN - 0 (Orphan Nuclear Receptors) RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - 0 (Retinoid X Receptors) RN - 0 (Sulfonamides) RN - 0 (T0901317) RN - 1UA8E65KDZ (Alitretinoin) RN - 5688UTC01R (Tretinoin) SB - IM MH - ATP Binding Cassette Transporter, Subfamily G, Member 1 MH - ATP-Binding Cassette Transporters/*genetics MH - Alitretinoin MH - Animals MH - Base Sequence MH - Cell Line MH - Cell Line, Tumor MH - DNA-Binding Proteins/agonists/*genetics MH - Electrophoretic Mobility Shift Assay MH - Hepatocytes/*metabolism MH - Humans MH - Hydrocarbons, Fluorinated MH - Liver X Receptors MH - Macrophages/*physiology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Molecular Sequence Data MH - Orphan Nuclear Receptors MH - Receptors, Cytoplasmic and Nuclear/agonists/*genetics MH - Response Elements/*genetics MH - Retinoid X Receptors/agonists MH - Sequence Alignment MH - Sulfonamides/pharmacology MH - Transcription Initiation Site MH - Tretinoin/pharmacology MH - Up-Regulation EDAT- 2005/07/19 09:00 MHDA- 2006/01/13 09:00 CRDT- 2005/07/19 09:00 PHST- 2005/07/19 09:00 [pubmed] PHST- 2006/01/13 09:00 [medline] PHST- 2005/07/19 09:00 [entrez] AID - S0022-2275(20)32906-0 [pii] AID - 10.1194/jlr.M500080-JLR200 [doi] PST - ppublish SO - J Lipid Res. 2005 Oct;46(10):2151-67. doi: 10.1194/jlr.M500080-JLR200. Epub 2005 Jul 16.