美国科学家近日开发出一种新的基因沉默技术,该技术可用于标靶那些会导致疾病的基因,并可为预防那些基因缺陷在其中发挥了作用的疾病铺平道路。相关论文8月17日在线发表于《自然—细胞生物学》(Nature Cell Biology)上。
领导此次研究的是美国西奈山医学院的Ming-Ming Zhou。研究人员发现,绿草履虫绿藻病毒(PBCV)利用病毒蛋白修改宿主DNA包装染色质,并转换宿主转录机器开关来进行病毒复制。基于这一发现,研究人员成功地开发出了一种新的基因打靶技术,能够有效地抑制人类细胞中目标基因的转录表达,其中包括一些与许多疾病的发作有关的基因。
Zhou说:“通过沉默某些基因,我们或许能够抑制那些会导致艾滋、癌症、发炎以及中枢和周围神经系统疾病的基因。我们现在知道能够聚焦于这些基因,并能够潜在地改变许多疾病的最终进程,而这些疾病正深刻地影响着人们的生活。”(生物谷Bioon.com)
生物谷推荐原始出处:
Nature Cell Biology,doi:10.1038/ncb1772,Shiraz Mujtaba,Ming-Ming Zhou
Epigenetic transcriptional repression of cellular genes by a viral SET protein
Shiraz Mujtaba1, Karishma L. Manzur1, James R. Gurnon2, Ming Kang2, James L. Van Etten2 & Ming-Ming Zhou1
Viruses recruit host proteins to secure viral genome maintenance and replication. However, whether they modify host histones directly to interfere with chromatin-based transcription is unknown. Here we report that Paramecium bursaria chlorella virus 1 (PBCV-1) encodes a functional SET domain histone Lys methyltransferase (HKMTase) termed vSET, which is linked to rapid inhibition of host transcription after viral infection. We show that vSET is packaged in the PBCV-1 virion, and that it contains a nuclear localization signal and probably represses host transcription by methylating histone H3 at Lys 27 (H3K27), a modification known to trigger gene silencing in eukaryotes. We also show that vSET induces cell accumulation at the G2/M phase by recruiting the Polycomb repressive complex CBX8 to the methylated H3K27 site in a heterologous system. vSET-like proteins that have H3K27 methylation activity are conserved in chlorella viruses. Our findings suggest a viral mechanism to repress gene transcription by direct modification of chromatin by PBCV-1 vSET.