Genomic structure and DNA binding properties of the human zinc finger transcriptional repressor AP-2rep (KLF12).
We recently cloned a novel murine transcriptional repressor, the Krüppel-like zinc finger protein AP-2rep (HGMW-approved symbol KLF12), that binds to a regulatory element in the AP-2alpha gene promoter. In the present study, we characterize the human AP-2rep homolog and describe expression patterns in human urogenital and lymphoma cell lines. The predicted human protein of 402 amino acids exhibits 95.8% identity and 98.5% similarity to the murine AP-2rep peptide. The genomic locus of human AP-2rep consists of seven exons and was assigned to chromosome 13q22 by fluorescence in situ hybridization to metaphase chromosomes. Human AP-2rep repressed both reporter expression from a transiently transfected AP-2alpha promoter and the endogenous AP-2alpha gene and inversely was negatively regulated by AP-2alpha. The consensus motif CAGTGGG was identified by an in vitro binding site selection assay. In summary, our data further point to an important role of AP-2rep as a transcriptional silencer and reveal reciprocal regulation of AP-2alpha and AP-2rep.
Roth
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Institute for Pathology, University of Regensburg Medical School, Franz-Josef-Strauss-Allee, Regensburg, D-93042, Germany.
Schuierer
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Günther
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Buettner
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D000595:Amino Acid Sequence; D000818:Animals; D002051:Burkitt Lymphoma / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D016384:Consensus Sequence; D004247:DNA / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D020868:Gene Silencing; D005796:Genes; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019169:Jurkat Cells / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology; D051741:Kruppel-Like Transcription Factors; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000502:physiology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D018243:Teratocarcinoma / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C436492:KLF12 protein, human; D051741:Kruppel-Like Transcription Factors; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D004247:DNA