Osborne Cameron S, Chakalova Lyubomira, Mitchell Jennifer A, Horton Alice, Wood Andrew L, Bolland Daniel J, Corcoran Anne E, Fraser Peter
Laboratory of Chromatin and Gene Expression, The Babraham Institute, Cambridge, United Kingdom.
PLoS Biol. 2007 Aug;5(8):e192. doi: 10.1371/journal.pbio.0050192.
Transcription in mammalian nuclei is highly compartmentalized in RNA polymerase II-enriched nuclear foci known as transcription factories. Genes in cis and trans can share the same factory, suggesting that genes migrate to preassembled transcription sites. We used fluorescent in situ hybridization to investigate the dynamics of gene association with transcription factories during immediate early (IE) gene induction in mouse B lymphocytes. Here, we show that induction involves rapid gene relocation to transcription factories. Importantly, we find that the Myc proto-oncogene on Chromosome 15 is preferentially recruited to the same transcription factory as the highly transcribed Igh gene located on Chromosome 12. Myc and Igh are the most frequent translocation partners in plasmacytoma and Burkitt lymphoma. Our results show that transcriptional activation of IE genes involves rapid relocation to preassembled transcription factories. Furthermore, the data imply a direct link between the nonrandom interchromosomal organization of transcribed genes at transcription factories and the incidence of specific chromosomal translocations.
哺乳动物细胞核中的转录高度分隔于富含RNA聚合酶II的核灶，即转录工厂。顺式和反式基因可共享同一转录工厂，这表明基因会迁移至预先组装好的转录位点。我们利用荧光原位杂交技术，研究了小鼠B淋巴细胞中即早（IE）基因诱导过程中基因与转录工厂关联的动态变化。在此，我们表明诱导过程涉及基因快速迁移至转录工厂。重要的是，我们发现15号染色体上的Myc原癌基因优先被招募至与位于12号染色体上高转录的Igh基因相同的转录工厂。Myc和Igh是浆细胞瘤和伯基特淋巴瘤中最常见的易位伙伴。我们的结果表明，IE基因的转录激活涉及快速迁移至预先组装好的转录工厂。此外，这些数据暗示转录工厂中转录基因的非随机染色体间组织与特定染色体易位的发生率之间存在直接联系。
