Arai Y, Hatano M, Tokuhisa T
Division of Developmental Genetics, Center for Biomedical Science, Chiba University School of Medicine, Japan.
Gene. 1997 Jul 1;193(1):73-9. doi: 10.1016/s0378-1119(97)00088-7.
The HOX11 gene was isolated from the chromosomal breakpoint of human T cell acute lymphoblastic leukemias with a chromosomal translocation t(10;14). Expression of this proto-oncogene is strictly controlled in normal tissues. However, regulatory elements of the gene have never been studied. Since the HOX11 gene is well conserved between human and murine, we sequenced 5' flanking region of the murine Hox11 gene and analyzed the elements. We identified the transcription start site (+1) of the gene using mRNA from fetal spleens by primer extension analysis. The start site was determined at 795 bp upstream from the ATG site. A typical TATA box sequence was found at 35 bp upstream from the start site. Furthermore, promoter activity of the 5' flanking region of the start site was monitored by luciferase assay. The activity mainly located within a 540-bp fragment immediately upstream from the start site (-540 to +1). The (-1240 to -540) region contained a negative regulatory element of the transcription. The TATA box sequence and the nucleotide sequence around the transcription start site were conserved in the human HOX11 gene. The transcription start site of the human HOX11 gene in normal tissues is discussed.
HOX11基因是从具有染色体易位t(10;14)的人类T细胞急性淋巴细胞白血病的染色体断点处分离出来的。该原癌基因在正常组织中的表达受到严格控制。然而，该基因的调控元件从未被研究过。由于HOX11基因在人和小鼠之间高度保守，我们对小鼠Hox11基因的5'侧翼区域进行了测序并分析了这些元件。我们通过引物延伸分析，使用来自胎脾的mRNA确定了该基因的转录起始位点(+1)。起始位点位于ATG位点上游795 bp处。在起始位点上游35 bp处发现了一个典型的TATA盒序列。此外，通过荧光素酶测定监测起始位点5'侧翼区域的启动子活性。活性主要位于起始位点上游紧邻的一个540 bp片段内(-540至+1)。(-1240至-540)区域包含转录的负调控元件。人类HOX11基因中TATA盒序列和转录起始位点周围的核苷酸序列是保守的。本文讨论了正常组织中人类HOX11基因的转录起始位点。
