Heiss N S, Gloeckner G, Bächner D, Kioschis P, Klauck S M, Hinzmann B, Rosenthal A, Herman G E, Poustka A
Department of Molecular Genome Analysis, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Genomics. 1997 Aug 1;43(3):329-38. doi: 10.1006/geno.1997.4810.
Construction of a transcript map in the DXS52 region in Xq28 had previously led to the isolation of a cDNA with a LIM zinc finger domain in the carboxyl terminus. In parallel, the orthologous murine transcript was isolated from the syntenic region. The human and mouse cDNAs have been designated ZNF185 and Zfp185, respectively. By integrating the cDNA sequence with the cosmid-derived genomic sequence the exon-intron structure of the 3' end of the ZNF185 gene was resolved. Comparative sequence analyses of the human genomic sequence with the full-length murine cDNA facilitated prediction of the 5' end of the gene. The selective expression of three transcripts corresponding to the ZNF185 gene and a related gene was shown by Northern and Southern blots. In situ hybridizations revealed a nonubiquitous and stage-specific expression of Zfp185, especially in differentiating connective tissue. Since LIM proteins regulate cellular proliferation and/or differentiation by diverse mechanisms, and some have directly been associated with disease, conceivably ZNF185 may represent a candidate for a disease-causing gene linked to Xq28. Knowledge of the genomic structure will permit detailed mutation analyses.
此前在Xq28的DXS52区域构建转录图谱时，已分离出一个在羧基末端带有LIM锌指结构域的cDNA。与此同时，从同区域的小鼠中分离出了直系同源转录本。人类和小鼠的cDNA分别被命名为ZNF185和Zfp185。通过将cDNA序列与黏粒衍生的基因组序列整合，解析了ZNF185基因3'端的外显子-内含子结构。通过对人类基因组序列与全长小鼠cDNA进行比较序列分析，有助于预测该基因的5'端。Northern和Southern印迹显示了与ZNF185基因及一个相关基因对应的三种转录本的选择性表达。原位杂交揭示了Zfp185的非普遍表达和阶段特异性表达，特别是在分化的结缔组织中。由于LIM蛋白通过多种机制调节细胞增殖和/或分化，并且一些已直接与疾病相关，因此可以想象ZNF185可能是与Xq28相关的致病基因的候选者。基因组结构的知识将有助于进行详细的突变分析。
