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人类锌指转录抑制因子AP-2rep(KLF12)的基因组结构与DNA结合特性

Genomic structure and DNA binding properties of the human zinc finger transcriptional repressor AP-2rep (KLF12).

作者信息

Roth C, Schuierer M, Günther K, Buettner R

机构信息

Institute for Pathology, University of Regensburg Medical School, Franz-Josef-Strauss-Allee, Regensburg, D-93042, Germany.

出版信息

Genomics. 2000 Feb 1;63(3):384-90. doi: 10.1006/geno.1999.6084.

DOI:10.1006/geno.1999.6084
PMID:10704285
Abstract

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.

摘要

我们最近克隆了一种新型小鼠转录抑制因子,即Krüppel样锌指蛋白AP-2rep(HGMW批准符号为KLF12),它可与AP-2α基因启动子中的调控元件结合。在本研究中,我们对人AP-2rep同源物进行了表征,并描述了其在人泌尿生殖系和淋巴瘤细胞系中的表达模式。预测的含402个氨基酸的人蛋白与小鼠AP-2rep肽的同一性为95.8%,相似性为98.5%。人AP-2rep的基因组位点由7个外显子组成,并通过对中期染色体的荧光原位杂交定位到染色体1q22。人AP-2rep既抑制瞬时转染的AP-2α启动子的报告基因表达,也抑制内源性AP-2α基因,反之,它受到AP-2α的负调控。通过体外结合位点筛选试验鉴定出共有基序CAGTGGG。总之,我们的数据进一步表明AP-2rep作为转录沉默因子的重要作用,并揭示了AP-2α与AP-2rep的相互调控。

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