Vikkula M, Metsäranta M, Syvänen A C, Ala-Kokko L, Vuorio E, Peltonen L
Department of Human Molecular Genetics, National Public Health Institute, Helsinki, Finland.
Biochem J. 1992 Jul 1;285 ( Pt 1)(Pt 1):287-94. doi: 10.1042/bj2850287.
Transcription of the type-II procollagen gene (COL2A1) is very specifically restricted to a limited number of tissues, particularly cartilages. In order to identify transcription-control motifs we have sequenced the promoter region and the first intron of the human and mouse COL2A1 genes. With the assumption that these motifs should be well conserved during evolution, we have searched for potential elements important for the tissue-specific transcription of the COL2A1 gene by aligning the two sequences with each other and with the available rat type-II procollagen sequence for the promoter. With this approach we could identify specific evolutionarily well-conserved motifs in the promoter area. On the other hand, several suggested regulatory elements in the promoter region did not show evolutionary conservation. In the middle of the first intron we found a cluster of well-conserved transcription-control elements and we conclude that these conserved motifs most probably possess a significant function in the control of the tissue-specific transcription of the COL2A1 gene. We also describe locations of additional, highly conserved nucleotide stretches, which are good candidate regions in the search for binding sites of yet-uncharacterized cartilage-specific transcription regulators of the COL2A1 gene.
II型胶原蛋白基因(COL2A1)的转录非常特异性地局限于有限数量的组织,尤其是软骨组织。为了鉴定转录控制基序,我们对人和小鼠COL2A1基因的启动子区域和第一个内含子进行了测序。基于这些基序在进化过程中应得到很好保守的假设,我们通过将人、小鼠这两个序列相互比对以及与现有的大鼠II型胶原蛋白基因启动子序列比对,来寻找对COL2A1基因组织特异性转录重要的潜在元件。通过这种方法,我们能够在启动子区域鉴定出特定的、进化上高度保守的基序。另一方面,启动子区域中一些推测的调控元件并未表现出进化保守性。在第一个内含子中部,我们发现了一组高度保守的转录控制元件,我们得出结论,这些保守基序很可能在COL2A1基因组织特异性转录的控制中具有重要功能。我们还描述了其他高度保守的核苷酸延伸片段的位置,这些区域是寻找COL2A1基因尚未鉴定的软骨特异性转录调节因子结合位点的良好候选区域。