Porsch-Özcürümez, Mustafa and Langmann, Thomas and Heimerl, Susanne and Borsukova, Hana and Kaminski, Wolfgang E. and Drobnik, Wolfgang and Honer, Christian and Schumacher, Christoph and Schmitz, Gerd (2001) The zinc finger protein 202 (ZNF202) is a transcriptional repressor of ATP binding cassette transporter A1 (ABCA1) and ABCG1 gene expression and a modulator of cellular lipid efflux. JOURNAL OF BIOLOGICAL CHEMISTRY, 276 (15). pp. 12427-12433. ISSN 0021-9258
Full text not available from this repository. (Request a copy)Abstract
The zinc finger gene 202 (ZNF202) located within a hypoalphalipoproteinemia susceptibility locus on chromosome 11q23 is a transcriptional repressor of various genes involved in lipid metabolism. To provide further evidence for a functional linkage between ZNF202 and hypoalphalipoproteinemia, we investigated the effect of ZNF202 expression on ATP binding cassette transporter A1 (ABCA1) and ABCG1, ABCA1 is a key regulator of the plasma high density lipoprotein pool size, whereas ABCG1 is another mediator of cellular cholesterol and phospholipid efflux in human macrophage. We demonstrate here that the full-length ZNF202m1 isoform binds to GnT repeats within the promoters of ABCA1 (-229/ -210) and ABCG1 (-572/-552), ZNF202m1 expression in HepG2 cells dose-dependently repressed the promotor activities of ABCA1 and ABCG1, This transcriptional effect required the presence of the SCAN domain in ZNF202 and the functional integrity of a TATA box at position -24 of ABCA1, whereas the presence of GnT binding motifs was nonessential. The state of ZNF202 SCAN domain oligomerization affected the ability of the adjacent ZNF202 Kruppel-associated box domain to recruit the transcriptional corepressor KAP1, Overexpression of ZNF202m1 in RAW264.7 macrophages prevented the induction of ABCA1 gene expression by 20(S)OH-cholesterol and 9-cis-retinoic acid, further substantiating the interference of ZNF202 in critical elements of transcriptional activation, Finally, HDL and apoAI-mediated lipid efflux was significantly reduced in RAW264.7 cells stably expressing ZNF202m1, In conclusion, we have identified ABCA1 and ABCG1 as target genes for ZNF202-mediated repression and thus, provide evidence for a functional linkage between ZNF202 and hypoalphalipoproteinemia.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TANGIER-DISEASE PATIENTS; DENSITY-LIPOPROTEIN; CHOLESTEROL EFFLUX; MOLECULAR-CLONING; PLASMA-MEMBRANE; APOA-I; PROMOTER; DOMAIN; COREPRESSOR; MACROPHAGES; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Feb 2022 16:57 |
| Last Modified: | 08 Feb 2022 16:57 |
| URI: | https://pred.uni-regensburg.de/id/eprint/41501 |
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