Patel B K, Keck C L, O'Leary R S, Popescu N C, LaRochelle W J
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Building 37 Room 1E24, Bethesda, Maryland, 20892, USA.
Genomics. 1998 Sep 1;52(2):192-200. doi: 10.1006/geno.1998.5436.
Stat6 signaling pathways have been correlated with functional responses induced by IL-4 and PDGF that may play a role in human malignancy. Utilizing fluorescence in situ hybridization, we mapped the human Stat6 gene to chromosome 12q bands 13.3-14.1, a breakpoint region implicated in a wide variety of solid tumors. To understand the genesis of three human Stat6 variant cDNAs, including a naturally occurring dominant negative species, we further characterized the genomic structure and flanking regions of the human Stat6 gene. The human Stat6 gene encompassed over 19 kb and contained 23 exons. For promoter studies, we introduced flanking sequence 5' of Stat6 exon 1 into a promoterless luciferase reporter vector and characterized basal promoter activity by deletion analysis. DNA sequence analysis revealed potential transcriptional regulation of the putative promoter through numerous consensus binding elements. Finally, we conclude that selective exon deletion and utilization of alternative donor/acceptor sites appear to explain best human Stat6 variant mRNAs.
Stat6信号通路已与IL-4和PDGF诱导的功能反应相关联，这些反应可能在人类恶性肿瘤中发挥作用。利用荧光原位杂交技术，我们将人类Stat6基因定位到12号染色体q带13.3 - 14.1区域，该区域是一个与多种实体瘤相关的断裂点区域。为了了解三种人类Stat6变异cDNA的起源，包括一种天然存在的显性负性物种，我们进一步对人类Stat6基因的基因组结构和侧翼区域进行了表征。人类Stat6基因全长超过19kb，包含23个外显子。对于启动子研究，我们将Stat6外显子1 5'端的侧翼序列导入无启动子的荧光素酶报告载体，并通过缺失分析来表征基础启动子活性。DNA序列分析揭示了通过众多共有结合元件对推定启动子的潜在转录调控。最后，我们得出结论，选择性外显子缺失和可变供体/受体位点的利用似乎最能解释人类Stat6变异mRNA的产生。
