Parslow T G, Blair D L, Murphy W J, Granner D K
Proc Natl Acad Sci U S A. 1984 May;81(9):2650-4. doi: 10.1073/pnas.81.9.2650.
Recent investigations have suggested that tissue-specific regulatory factors are required for immunoglobulin gene transcription. Cells of the mouse lymphocytoid pre-B-cell line 70Z/3 contain a constitutively rearranged immunoglobulin kappa light chain gene; the nucleotide sequence of this gene exhibits all the known properties of a functionally competent transcription unit. Nevertheless, transcripts derived from this gene are detectable only after exposure of the cells to bacterial lipopolysaccharide, implying that accurate DNA rearrangement is not sufficient to activate expression of the gene. Comparison of the sequence of the 70Z/3 kappa light chain gene with those encoding other immunoglobulin heavy and light chains has revealed that a distinctive promoter region structure is characteristic of this multigene family. The sequence A-T-T-T-G-C-A-T lies approximately 70 base pairs upstream from the site of transcriptional initiation in every light chain gene examined; in heavy chain genes, the corresponding location is occupied by the precise inverse (A-T-G-C-A-A-A-T) of this sequence. Although adjacent regions of DNA have diverged extensively in evolution, these octanucleotide sequences are stringently conserved at this location among diverse immunoglobulin genes from at least two mammalian species. The proximity of this conserved octanucleotide block to the site of transcriptional initiation suggests that it may serve as a recognition locus for factors regulating immunoglobulin gene expression in a tissue-specific fashion.
最近的研究表明，免疫球蛋白基因转录需要组织特异性调节因子。小鼠淋巴细胞前B细胞系70Z/3的细胞含有一个组成性重排的免疫球蛋白κ轻链基因；该基因的核苷酸序列展现出一个功能上有活性的转录单位的所有已知特性。然而，只有在细胞暴露于细菌脂多糖后，才能检测到源自该基因的转录本，这意味着精确的DNA重排不足以激活该基因的表达。将70Z/3 κ轻链基因的序列与编码其他免疫球蛋白重链和轻链的序列进行比较后发现，独特的启动子区域结构是这个多基因家族的特征。在所检测的每个轻链基因中，序列A-T-T-T-G-C-A-T位于转录起始位点上游约70个碱基对处；在重链基因中，该序列的精确反向序列（A-T-G-C-A-A-A-T）占据了相应位置。尽管DNA的相邻区域在进化过程中已经广泛分化，但在来自至少两个哺乳动物物种的不同免疫球蛋白基因中，这些八核苷酸序列在该位置上严格保守。这个保守的八核苷酸块与转录起始位点的接近表明，它可能作为以组织特异性方式调节免疫球蛋白基因表达的因子的识别位点。
