The E-box motif in the proximal ABCA1 promoter mediates transcriptional repression of the ABCA1 gene
2002
Details
- Autor(en) / Beteiligte
- Titel
- The E-box motif in the proximal ABCA1 promoter mediates transcriptional repression of the ABCA1 gene
- Ist Teil von
- Journal of lipid research, 2002-02, Vol.43 (2), p.297-306
- Ort / Verlag
- United States: Elsevier
- Erscheinungsjahr
- 2002
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- To identify regulatory elements in the proximal human ATP-binding cassette transporter A1 (hABCA1) gene promoter we transfected RAW cells with plasmids containing mutations in the E-box, AP1, and liver X receptor (LXR) elements as well as the two Sp1 motifs. Point mutations in either Sp1 site or in the AP1 site had only a minor effect whereas mutation of the LXR element decreased promoter activity. In contrast, mutation or deletion of the E-box motif caused a 3-fold increase in transcriptional activity under basal conditions. Gel shift and DNaseI footprint analysis showed binding of a protein or protein complex to this region. Preincubation of nuclear extracts with antibodies established that USF1, USF2, and fos related antigen (Fra) 2 bind to DNA sequences in the human ABCA1 promoter that contains the intact E-box but not the mutant or deleted E-box. Co-transfection of USF1 and USF2 enhanced, but Fra2 repressed, ABCA1 promoter activity. Thus, a complex consisting of USF1, USF2, and Fra2 binds the E-box motif 147 bp upstream of the transcriptional start site and facilitates repression of the human ABCA1 promoter. These combined studies identify a novel site in the human ABCA1 promoter involved in the regulation of ABCA1 gene expression.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0022-2275eISSN: 1539-7262DOI: 10.1016/s0022-2275(20)30172-3Titel-ID: cdi_doaj_primary_oai_doaj_org_article_0a5a7f5833844f6cab090a3b646b1d62
- Format
- –
- Schlagworte
- Animals, ATP Binding Cassette Transporter 1, ATP-binding cassette transporter, ATP-Binding Cassette Transporters - biosynthesis, ATP-Binding Cassette Transporters - genetics, Binding Sites, Cells, Cultured, DNA-Binding Proteins - metabolism, DNA-Binding Proteins - physiology, E-box, E-Box Elements - genetics, Fos-Related Antigen-2, Gene Expression Regulation, high density lipoproteins, Humans, Mice, Mutation, Promoter Regions, Genetic, Regulatory Sequences, Nucleic Acid, Transcription Factors - metabolism, Transcription Factors - physiology, Transcription, Genetic, Upstream Stimulatory Factors