Chromosome translocations clustered 5' of the murine c-myc gene qualitatively affect promoter usage: implications for the site of normal c-myc regulation.
Chromosome translocations clustered 5' of the murine c-myc gene qualitatively affect promoter usage: implications for the site of normal c-myc regulation.
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小鼠 c-myc 基因 5 处聚集的染色体易位定性地影响启动子的使用：对正常 c-myc 调节位点的影响。
DOI：
10.1002/j.1460-2075.1985.tb03800.x
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Marcu,KB
中科院分区：
文献类型：
--
作者：
Yang,JQ;Bauer,SR;Mushinski,JF;Marcu,KB
描述了5例新型小鼠浆细胞（PC）肿瘤，其第一个c-myc外显子的染色体易位为350 - 500 bp 5′。TEPC 1194、ABPC 33和TEPC 1165的t（12;15）s分别位于Cu、C γ 2a和C α IgCH基因的完整c-myc位点5′。在ABPC 17中，IgH增强子元件和相邻开关（Su）序列位于第一个c-myc外显子的5′端，而该增强子与TEPC 1194、ABPC 33和TEPC 1033易位的相互产物相关。定量S1核酸酶分析表明，在这五种肿瘤中，两种c-myc启动子（P1和P2）的转录比例增加了4至7倍。除了TEPC 1165（其在外显子1中含有小的缺失）之外，与没有这种启动子移位的其他肿瘤相比，P1：P2比率的这种增加似乎表现为P2使用的减少。对另外27个PC和非PC B淋巴肿瘤和细胞系的调查显示，这种幅度的myc启动子移位是具有5′近端易位的PC肿瘤所特有的。我们提出：（i）这些成簇的断裂点确定了位于c-myc外显子1至少350 bp 5′的正常c-myc调控元件;（ii）该顺式作用上游元件的缺失或破坏以及c-myc与IgCH位点的连接将导致该癌基因在这些以及大多数其他PC肿瘤中的异常表达。
Five novel murine plasma cell (PC) tumors with chromosome translocations 350‐500 bp 5′ of the first c‐myc exon are described. The t(12;15)s of TEPC 1194, ABPC 33 and TEPC 1165 position the intact c‐myc locus 5′ of the Cu, C gamma 2a and C alpha IgCH genes respectively. In ABPC 17, the IgH enhancer element and adjacent switch (Su) sequences were found 5′ of the first c‐myc exon while this enhancer is associated with the reciprocal products of the TEPC 1194, ABPC 33 and TEPC 1033 translocations. Quantitative S1 nuclease analyses demonstrate that the ratios of transcription from the two c‐myc promoters (P1 and P2) are increased 4‐to 7‐fold in these five tumors. With the exception of TEPC 1165, (which contains a small deletion in exon 1), such increases in P1:P2 ratios appear to be manifested by a reduction in P2 usage in comparison to other tumors without such promoter shifts. A survey of 27 additional PC and non‐PC B lymphoid tumors and cell lines revealed that myc promoter shifts of this magnitude are unique to PC tumors with 5′‐proximal translocations. We propose that (i) these clustered breakpoints identify a normal c‐myc regulatory element located at least 350 bp 5′ of c‐myc exon 1; (ii) the loss or disruption of this cis‐acting upstream element and the linkage of c‐myc to the IgCH locus would result in abnormal expression of this oncogene in these as well as most other PC tumors.