c-Myc binds to human ribosomal DNA and stimulates transcription of rRNA genes by RNA polymerase I
c-Myc binds to human ribosomal DNA and stimulates transcription of rRNA genes by RNA polymerase I
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DOI：
10.1038/ncb1224
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发表时间：
2005-03-01
影响因子：
21.3
通讯作者：
White, RJ
中科院分区：
文献类型：
--
作者：
Grandori, C;Gomez-Roman, N;White, RJ
c-Myc通过涉及RNA聚合酶（Pol） II和Pol iii转录基因的转录程序来协调细胞生长和分裂。在这里，我们证明了人类c-Myc也直接增强核糖体RNA （rRNA）基因的Pol I转录。在条件MYC-ER等位基因（编码myc -雌激素受体融合蛋白）激活后，rRNA的合成和积累迅速发生，对Pol II转录抑制具有抗性，并被c-MYC RNA干扰显著减少。此外，通过联合免疫荧光和rRNA-FISH，我们在活性核糖体DNA （rDNA）转录位点的核仁中检测到内源性c-Myc。我们的数据还表明，c-Myc与位于人类rDNA中的特定共识元件结合，并与Pol - i特异性因子SL1相关。c-Myc在rDNA上特定位点的存在与SL1向rDNA启动子的募集以及组蛋白乙酰化的增加相一致。我们认为，通过c-Myc刺激rRNA合成是驱动细胞生长和肿瘤发生的关键途径。
c-Myc coordinates cell growth and division through a transcriptional programme that involves both RNA polymerase (Pol) II- and Pol III-transcribed genes. Here, we demonstrate that human c-Myc also directly enhances Pol I transcription of ribosomal RNA ( rRNA) genes. rRNA synthesis and accumulation occurs rapidly following activation of a conditional MYC-ER allele ( coding for a Myc-oestrogen-receptor fusion protein), is resistant to inhibition of Pol II transcription and is markedly reduced by c-MYC RNA interference. Furthermore, by using combined immunofluorescence and rRNA-FISH, we have detected endogenous c-Myc in nucleoli at sites of active ribosomal DNA ( rDNA) transcription. Our data also show that c-Myc binds to specific consensus elements located in human rDNA and associates with the Pol I-specific factor SL1. The presence of c-Myc at specific sites on rDNA coincides with the recruitment of SL1 to the rDNA promoter and with increased histone acetylation. We propose that stimulation of rRNA synthesis by c-Myc is a key pathway driving cell growth and tumorigenesis.