CpG-island promoters drive transcription of human telomeres
CpG-island promoters drive transcription of human telomeres
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DOI：
10.1261/rna.1748309
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发表时间：
2009-12-01
期刊：
影响因子：
4.5
通讯作者：
Azzalin, Claus M.
中科院分区：
文献类型：
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作者：
Nergadze, Solomon G.;Farnung, Benjamin O.;Azzalin, Claus M.
端粒是线性真核染色体的异染色质末端，长期以来的观点认为端粒在转录上是沉默的，但DNA依赖的RNA聚合酶II（RNAPII）将端粒DNA转录为含端粒重复序列的RNA（TERRA）这一发现推翻了该观点。在此，我们表明多个人类染色体末端共有的富含CpG二核苷酸的DNA岛促进TERRA分子的转录。TERRA启动子维持报告基因的细胞内表达，位于TERRA转录起始位点的紧邻上游，并且在体内与有活性的RNAPII结合。最后，所鉴定的启动子CpG二核苷酸在体内被甲基化，并且胞嘧啶甲基化对TERRA的丰度起负调控作用。亚端粒启动子的存在驱动来自独立染色体末端的TERRA转录，这支持了TERRA在端粒生物学背景下发挥基本功能的观点。
The longstanding dogma that telomeres, the heterochromatic extremities of linear eukaryotic chromosomes, are transcriptionally silent was overturned by the discovery that DNA-dependent RNA polymerase II (RNAPII) transcribes telomeric DNA into telomeric repeat-containing RNA (TERRA). Here, we show that CpG dinucleotide-rich DNA islands, shared among multiple human chromosome ends, promote transcription of TERRA molecules. TERRA promoters sustain cellular expression of reporter genes, are located immediately upstream of TERRA transcription start sites, and are bound by active RNAPII in vivo. Finally, the identified promoter CpG dinucleotides are methylated in vivo, and cytosine methylation negatively regulates TERRA abundance. The existence of subtelomeric promoters, driving TERRA transcription from independent chromosome ends, supports the idea that TERRA exerts fundamental functions in the context of telomere biology.