Activation of a translocated c-myc gene: role of structural alterations in the upstream region.
Activation of a translocated c-myc gene: role of structural alterations in the upstream region.
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易位 c-myc 基因的激活：上游区域结构改变的作用。
DOI：
10.1073/pnas.81.21.6798
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发表时间：
1984
影响因子：
11.1
通讯作者：
Hayward,WS
中科院分区：
文献类型：
--
作者：
Wiman,KG;Clarkson,B;Hayday,AC;Saito,H;Tonegawa,S;Hayward,WS
携带8;14易位的Burkitt淋巴瘤细胞系AW-Ramos中易位的c-myc基因的表达水平比淋巴母细胞系中的c-myc高2至5倍。易位事件将c-myc连接到IgM转换区。因此，最近鉴定的免疫球蛋白转录增强子元件不与易位的c-myc基因相连。染色体重组发生在c-myc 5'帽位点上游约等于340个核苷酸处，使所有三个c-myc外显子保持完整。易位的c-myc基因的两个编码外显子的核苷酸序列与正常c-myc基因的核苷酸序列相同。第一，非编码c-myc外显子和该外显子和染色体重组点之间的区域的核苷酸序列分析揭示了两个单碱基的差异，从正常的c-myc。我们的数据表明，AW-Ramos细胞中c-myc的激活是由表达改变而不是基因产物改变引起的，这是由于位于c-myc上游340个核苷酸以上的调节序列的丢失或正常c-myc调节的破坏造成的。一个或两个碱基取代。或者，在IG基因座中未鉴定的增强子样序列可能改变c-myc的表达。
The translocated c-myc gene in AW-Ramos, a Burkitt lymphoma cell line carrying the 8;14 translocation, is expressed at 2- to 5-fold higher levels than c-myc in lymphoblastoid cell lines. The translocation event has joined c-myc to the IgM switch region. As a consequence, a recently identified immunoglobulin transcriptional enhancer element is not linked to the translocated c-myc gene. Chromosomal recombination occurs approximately equal to 340 nucleotides upstream of the c-myc 5' cap site, leaving all three c-myc exons intact. The nucleotide sequences of the two coding exons in the translocated c-myc gene are identical to those of the normal c-myc gene. Nucleotide sequence analyses of the first, noncoding c-myc exon and of the region between this exon and the chromosomal recombination point reveal two single-base differences from normal c-myc. Our data indicate that altered expression rather than an altered gene product is responsible for c-myc activation in AW-Ramos cells and that this is a result of either loss of regulatory sequences located greater than 340 nucleotides upstream of c-myc or disruption of normal c-myc regulation by one or both base substitutions. Alternatively, unidentified enhancer-like sequences in the Ig locus may alter the expression of c-myc.