The block to transcription elongation is promoter dependent in normal and Burkitt's lymphoma c-myc alleles.
The block to transcription elongation is promoter dependent in normal and Burkitt's lymphoma c-myc alleles.
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在正常和伯基特淋巴瘤 c-myc 等位基因中，转录延伸的阻断是启动子依赖性的。
DOI：
10.1101/gad.4.1.75
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发表时间：
1990
影响因子：
10.5
通讯作者：
Groudine,M
中科院分区：
文献类型：
--
作者：
Spencer,CA;LeStrange,RC;Novak,U;Hayward,WS;Groudine,M
人类Burkitt淋巴瘤细胞中存在c-myc异常表达模式，其持续表现为c-myc染色体易位、易位等位基因内部和侧翼突变、外显子1转录延长阻断丢失以及启动子转向使用上游P1启动子。为了确定Burkitt‘s淋巴瘤c-myc基因转录延伸受阻丧失和导致c-myc失控的机制，我们分析了将正常和Burkitt淋巴瘤c-myc等位基因转移到小鼠细胞和非洲爪哇卵母细胞生发泡后的转录模式。我们已经确定，尽管几个Burkitt淋巴瘤c-myc等位基因内部和周围的突变本身不足以消除转录延伸阻断，但P2启动子的转录启动可能是获得转录延伸阻断所必需的。为了直接测试c-myc启动子在编程转录延伸阻断中的作用，我们分析了包含P1或P2启动子缺失的体外诱变的c-myc基因的转录模式。这些数据证实，P1启动的c-myc转录本不会终止于外显子1 3‘端附近的离散位点，而P2启动的转录本要么终止，要么阅读转录阻断信号。因此，c-myc P1启动子的过度表达和/或结构性表达可能有助于提高Burkitt淋巴瘤细胞的直读转录，从而导致c-myc稳态转录的异常表达模式或水平。此外，正常细胞调节c-myc P2启动的转录以通读或阻止延伸的能力为c-myc稳定状态RNA水平提供了一种精细的控制机制。
Aberrant c-myc expression patterns occur in human Burkitt's lymphoma cells, which consistently exhibit c-myc chromosomal translocations, mutations within and flanking the translocated allele, a loss of the block to transcription elongation in exon 1, and a promoter shift to use of the upstream P1 promoter. To define the mechanism responsible for the loss of transcription elongation blockage and resulting c-myc deregulation in Burkitt's lymphoma, we analyzed transcription patterns after transfer of normal and Burkitt's lymphoma c-myc alleles into murine cells and Xenopus oocyte germinal vesicles. We have determined that although the mutations within and surrounding several Burkitt's lymphoma c-myc alleles are not sufficient, in themselves, to abrogate the transcription elongation block, transcription initiation from the P2 promoter may be necessary to obtain the block to transcription elongation. To test directly the role of c-myc promoters in programming transcription elongation blockage, we analyzed transcription patterns from in vitro mutagenized c-myc genes containing deletions of either the P1 or P2 promoter. These data confirm that P1-initiated c-myc transcripts do not terminate at discrete sites near the 3' end of exon 1, whereas P2-initiated transcripts either terminate or read through the transcription block signals. Therefore, overexpression and/or constitutive expression from the c-myc P1 promoter may contribute to increased readthrough transcription in Burkitt's lymphoma cells and, hence, to aberrant expression patterns or levels of c-myc steady-state transcripts. In addition, the ability of normal cells to modulate c-myc P2-initiated transcription to either read through or to block elongation provides a fine control mechanism over c-myc steady-state RNA levels.