STRUCTURE OF THE 5' ENDS OF IMMUNOGLOBULIN GENES - A NOVEL CONSERVED SEQUENCE

STRUCTURE OF THE 5' ENDS OF IMMUNOGLOBULIN GENES - A NOVEL CONSERVED SEQUENCE
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DOI:
10.1073/pnas.81.9.2650
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发表时间:
1984-01-01
期刊:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子:
--
通讯作者:
GRANNER, DK
GRANNER, DK
中科院分区:
其他
文献类型:
--
作者:
PARSLOW, TG;BLAIR, DL;GRANNER, DK

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显然,Ig 基因转录需要组织特异性调节因子。小鼠淋巴细胞样前B细胞系70Z/3的细胞含有组成型重排的Ig.κ。 L链基因;该基因的核苷酸序列表现出功能性转录单元的所有已知特性。然而,只有在将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,这意味着准确的 DNA 重排不足以激活该基因的表达。 70Z/3 .kappa 的序列比较。 L 链基因与编码其他 Ig H 和 L 链的基因揭示了独特的启动子区域结构是该多基因家族的特征。序列 A-T-T-T-G-C-A-T 位于 .apprx。每个检查的 L 链基因转录起始位点上游 70 个碱基对;在H链基因中,相应的位置被该序列的精确逆序列(A-T-G-C-A-A-A-T)占据。尽管 DNA 的相邻区域在进化过程中存在广泛差异,但这些八核苷酸序列在来自至少 2 个哺乳动物物种的不同 Ig 基因中严格保守。这个保守的八核苷酸块与转录起始位点的接近表明它可以作为以组织特异性方式调节 Ig 基因表达的因子的识别位点。
Apparently, tissue-specific regulatory factors are required for Ig gene transcription. Cells of the mouse lymphocytoid pre-B-cell line 70Z/3 contain a constitutively rearranged Ig .kappa. L 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. L chain gene with those encoding other Ig H and L 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 .apprx. 70 base pairs upstream from the site of transcriptional initiation in every L chain gene examined; in H 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 seqeunces are stringently conserved at this location among diverse Ig genes from at least 2 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 Ig gene expression in a tissue-specific fashion.