Disease relevance of ZNF202

• Based on the linkage and apparent transcriptional function of ZNF202, we propose that ZNF202 is a candidate susceptibility gene for human dyslipidemia [1].
• We tested the hypothesis that a common variant in ZNF202, A154V, predicts risk of ischemic heart disease (IHD), myocardial infarction (MI), and ischemic cerebrovascular disease (ICVD) [2].
• However, mutation analysis of 39 breast cancer samples revealed no evidence of mutations, indicating that ZNF202 is unlikely to be involved in the pathogenesis of this neoplasm [3].

High impact information on ZNF202

• PURPOSE OF REVIEW: The zinc finger protein ZNF202 is a transcriptional repressor controlling promoter elements predominantly found in genes involved in lipid metabolism and energy homeostasis [4].
• Furthermore, we provide an interlink between transcriptional repression by ZNF202 and enhancement of gene activation via nuclear receptor coactivation by SCAN domain protein 1 [4].
• 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 [5].
• 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 [5].
• Biochemical binding studies confirmed the associations of ZNF191 and SDP1 with ZNF202 and established the SCAN domain as a selective hetero- and homotypic oligomerization domain [6].

Biological context of ZNF202

• 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 [5].
• Here we show that the ZNF202 gene product is a transcriptional repressor that binds to elements found predominantly in genes that participate in lipid metabolism [1].
• Conversely, deloading of macrophage foam cells with HDL3 caused upregulation of ZNF202 mRNA [7].
• To further characterize the transcriptional regulation of the ZNF202 gene, comparative genomic sequence analysis and reporter gene assays were performed [7].
• The ZNF202 core promoter region resides within 247 bp upstream of the transcription initiation site and is highly active in THP-1 monocytes, yet downregulated upon macrophage differentiation [7].

Anatomical context of ZNF202

• OBJECTIVE: Zinc Finger Protein 202 (ZNF202) is a transcriptional repressor of genes affecting the vascular endothelium as well as lipid metabolism [2].
• Antibody supershift with a 22-bp DNA probe and nuclear extract from a Sertoli cell line demonstrated that a testis-specific zinc finger protein, ZNF202, might be one of the binding proteins [8].
• Western blots using ZNF202 antibody and Southwestern blot analyses with the DNA probe detected the same 60kDa protein in both Sertoli and ovarian granulosa cell lines [8].

Associations of ZNF202 with chemical compounds

• The ZNF202 gene resides in a chromosomal region linked genetically to low high density lipoprotein cholesterol in Utah families [1].

Regulatory relationships of ZNF202

• ZNF202 is inversely regulated with its target genes ABCA1 and apoE during macrophage differentiation and foam cell formation [7].
• Transfection studies indicated that ZNF202 repressed ovine FSHR promoter activity whereas RREB-1 was likely to function as an activator [8].

Other interactions of ZNF202

• In a yeast two-hybrid experiment using the zinc-finger transcription factor ZNF202 as bait, we previously identified the SCAN-domain-containing protein SDP1 [9].
• Upregulation of ABCA1, ABCG1, and apoE expression during monocyte differentiation and foam cell formation was accompanied by a simultaneous downregulation of both ZNF202 mRNA isoforms m1 and m3 [7].

Analytical, diagnostic and therapeutic context of ZNF202

• Using site-directed mutagenesis, we show that two highly conserved transcription factor binding sites, a GC-box and an Ets-binding motif, are required for ZNF202 gene expression [7].
• Molecular cloning and characterization of ZNF202: a new gene at 11q23.3 encoding testis-specific zinc finger proteins [3].

References