Micronuclei bearing acentric extrachromosomal chromatin are transcriptionally competent and may perturb the cancer cell phenotype
Micronuclei bearing acentric extrachromosomal chromatin are transcriptionally competent and may perturb the cancer cell phenotype
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DOI：
10.1158/1541-7786.mcr-07-0031
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发表时间：
2007-07-01
影响因子：
5.2
通讯作者：
Shimizu, Noriaki
中科院分区：
文献类型：
--
作者：
Utani, Koh-ichi;Kawamoto, June-ko;Shimizu, Noriaki
染色体外双微体（DM）携带导致人类癌细胞恶性化的扩增基因。DM的一种新的细胞内行为导致它们选择性地截留在微核内;如果位于DM上的基因在微核中表达，这可能会扰乱癌细胞表型。在这里，使用荧光原位杂交，我们检测到的成绩单DM富集微核。DM及其在活细胞中的转录物的可视化显示，DM在微核和细胞核中转录活跃。此外，在微核中检测到脉冲掺入的溴尿苷，并且转录物最终从微核中退出，类似于核转录物的行为。这种明显正常的基因表达模式，在DM富集的微核被限制到与核纤层蛋白13，核纤层蛋白B协会是更频繁的微核，纳入DM比那些纳入染色体arm. The频率核纤层蛋白13相关的微核进入S期后增加，因此，有一个伴随的增加，在微核的转录。综上所述，这些结果表明，DM上的基因表达可以通过掺入微核而暂时改变。这可能是相关的其他染色体外元素的广谱。
Extrachromosomal double minutes (DM) bear amplified genes that contribute to the malignancy of human cancer cells. A novel intracellular behavior of DMs resulted in their selective entrapment within micronuclei; opening the vista, this could perturb the cancer cell phenotype if genes located on DMs were expressed in micronuclei. Here, using fluorescence in situ hybridization, we detected transcripts in DM-enriched micronuclei. Visualization of DMs and their transcripts in live cells showed that DMs are as actively transcribed in the micronuclei and nuclei. Moreover, pulse-incorporated bromouridine was detected in the micronuclei, and the transcripts eventually exited from the micronuclei, similar to the behavior of nuclear transcripts. This apparently normal pattern of gene expression in DM-enriched micronuclei was restricted to micronuclei associated with lamin 13, and lamin B association was more frequent for micronuclei that incorporated DMs than for those that incorporated a chromosome arm. The frequency of lamin 13-associated micronuclei increased after entry into S phase, and accordingly, there was a concomitant increase in transcription in micronuclei. Taken together, these results indicate that the expression of genes on DMs can be temporally altered by their incorporation into micronuclei. This may be relevant for a broad spectrum of other extrachromosomal elements.