DNA sequence of the murine gamma 1 switch segment reveals novel structural elements.

DNA sequence of the murine gamma 1 switch segment reveals novel structural elements.
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DOI:
10.4049/jimmunol.136.7.2674
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发表时间:
1986-04
影响因子:
4.4
通讯作者:
M. Mowatt;W. Dunnick
M. Mowatt;W. Dunnick
中科院分区:
医学2区
文献类型:
--
作者:
M. Mowatt;W. Dunnick

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免疫球蛋白重链转换区是被认为在介导B淋巴细胞的类别转换中重要的DNA片段。尽管这些片段在不同的鼠同种型中长度不同,但它们的结构组织方案都是基于单元序列的串联重复。我们以前表明,S γ 1段意外地包含序列元素,显着不同于其普遍的单位重复(49聚体)。在这里,我们通过确定从BALB/c DNA克隆的S γ 1片段的完整核苷酸序列来扩展这种初步表征。我们发现,S γ 1由超过120个串联重复的49聚体组成。此外,我们表明,以前确定的非49聚体序列的一部分,直接重复元件约350 bp的长度(DR II),存在于两个拷贝的5'端的S γ 1。我们还发现在S γ 1的5'和3'端附近存在另一个约500 bp长的不相关的直接重复元件(DR I)。因此,S γ 1片段的结构可以缩写为5 ′-DRII-(49聚体)15-DRI-DRII-(49聚体)n-DRI,其中n在40和160之间。我们的Southern杂交实验结果表明,这种基本的结构方案是保持在8个不同的Igh单倍型,虽然在不同的Igh单倍型的S γ 1段包括不同数量的49聚体元件。其他鼠S γ片段在各种Igh基因座之间大小不同,但程度小于S γ 1。在串联重复序列的水平上,S gamma 1、S gamma 3和S gamma 2b代表三个不同的、不重叠的序列集。
Immunoglobulin heavy chain switch regions are segments of DNA considered to be important in mediating class switching in B lymphocytes. Whereas these segments vary in length among the different murine isotypes, their structural organization schemes are all based on the tandem repetition of unit sequences. We previously showed that the S gamma 1 segment unexpectedly contains sequence elements that differ significantly from its prevalent unit repeat (49mer). Here we extend this preliminary characterization by determining the complete nucleotide sequence of the cloned S gamma 1 segment from BALB/c DNA. We find that S gamma 1 consists of more than 120 tandemly repeated 49mers. In addition, we show that the previously identified non-49mer sequences are part of a direct repeat element about 350 bp in length (DR II), which exists in two copies at the 5' end of S gamma 1. We also show that another unrelated direct repeat element about 500 bp long (DR I) exists near the 5' and 3' ends of S gamma 1. Thus, the structure of the S gamma 1 segment might be may be abbreviated as 5'-DRII-(49mer)15-DRI-DRII-(49mer)n-DRI , where n is between 40 and 160. Our results of Southern hybridization experiments suggest that this basic structural scheme is maintained in eight different Igh haplotypes, although S gamma 1 segments in different Igh haplotypes include different numbers of 49mer elements. Other murine S gamma segments differ in size among various Igh loci, but to a lesser extent than S gamma 1. At the level of tandemly repeated sequences, S gamma 1, S gamma 3, and S gamma 2b represent three distinct, nonoverlapping sets of sequences.