Hammond-Kosack M C, Dobrinski B, Lurz R, Docherty K, Kilpatrick M W
Department of Clinical Genetics, University of Birmingham, Birmingham Maternity Hospital, UK.
Nucleic Acids Res. 1992 Jan 25;20(2):231-6. doi: 10.1093/nar/20.2.231.
Regulation of transcription of the human insulin gene appears to involve a series of DNA sequences in the 5' region. Hypersensitivity to DNA structural probes has previously been demonstrated in regulatory regions of cloned genomic DNA fragments, and been correlated with gene activity. To investigate the structure of the DNA in the human insulin gene, bromoacetaldehyde and S1 nuclease were reacted with a supercoiled plasmid containing a 5kb genomic insulin fragment. Both probes revealed the human insulin gene linked polymorphic region (ILPR), a region (-363) upstream of the transcriptional start site which contains multiple repeats of a 14-15mer oligonucleotide with the consensus sequence ACAGGGGT(G/C)(T/C)GGGG, as the major hypersensitive site. Fine mapping and electron microscopic analysis both show a very different behaviour of the two DNA strands in the region of the ILPR and suggest the G-rich strand may be adopting a highly structured conformation with the complementary strand remaining largely single stranded.
人类胰岛素基因的转录调控似乎涉及5'区域的一系列DNA序列。先前已在克隆的基因组DNA片段的调控区域中证明了对DNA结构探针的超敏反应，并与基因活性相关。为了研究人类胰岛素基因中DNA的结构，将溴乙醛和S1核酸酶与含有5kb基因组胰岛素片段的超螺旋质粒反应。两种探针均显示人类胰岛素基因连锁多态性区域（ILPR），即转录起始位点上游（-363）的一个区域，该区域包含14-15聚体寡核苷酸的多个重复序列，共有序列为ACAGGGGT(G/C)(T/C)GGGG，作为主要的超敏位点。精细定位和电子显微镜分析均显示ILPR区域中两条DNA链的行为非常不同，并表明富含G的链可能采用高度结构化的构象，而互补链在很大程度上保持单链状态。
