Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, Leiden, The Netherlands.
Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands.
Curr Issues Mol Biol. 2018;26:15-32. doi: 10.21775/cimb.026.015. Epub 2017 Sep 7.
The epigenome is a heritable layer of information not encoded in the DNA sequence of the genome, but in chemical modifications of DNA or histones. These chemical modifications, together with transcription factors, operate as spatiotemporal regulators of genome activity. Dissecting epigenome function requires controlled site-specific alteration of epigenetic information. Such control can be obtained using designed DNA-binding platforms associated with effector domains to function as targeted transcription factors or epigenetic modifiers. Here, we review the use of dCas9 as a novel and versatile tool for fundamental studies on epigenetic landscapes, chromatin structure and transcription regulation, and the potential of this approach in basic research in these fields.
表观基因组是一层遗传信息,它不编码在基因组的 DNA 序列中,而是编码在 DNA 或组蛋白的化学修饰中。这些化学修饰与转录因子一起,作为基因组活性的时空调节因子发挥作用。解析表观基因组功能需要对表观遗传信息进行受控的、特异性的改变。这种控制可以通过与效应结构域相关联的设计 DNA 结合平台来获得,这些平台可以作为靶向转录因子或表观遗传修饰物发挥作用。在这里,我们回顾了 dCas9 的使用,将其作为研究表观基因组景观、染色质结构和转录调控的基础的新型多功能工具,并讨论了这种方法在这些领域的基础研究中的潜力。