Gray Jesse M, Kim Tae-Kyung, West Anne E, Nord Alex S, Markenscoff-Papadimitriou Eirene, Lomvardas Stavros
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115,
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas 75390.
J Neurosci. 2015 Oct 14;35(41):13819-26. doi: 10.1523/JNEUROSCI.2622-15.2015.
Sprinkled throughout the genome are a million regulatory sequences called transcriptional enhancers that activate gene promoters in the right cells, at the right time. Enhancers endow the brain with its incredible diversity of cell types and also translate neural activity into gene induction. Thanks to rapid advances in genomic technologies, it is now possible to identify thousands of enhancers rapidly, test their transcriptional function en masse, and address their neurobiological functions via genome editing. Enhancers also promise to be a great technological opportunity for neuroscience, offering the potential for cell-type-specific genetic labeling and manipulation without the need for transgenesis. The objective of this review and the accompanying 2015 SfN mini-symposium is to highlight the use of new and emerging genomic technologies to probe enhancer function in the nervous system.
Transcriptional enhancers turn on genes in the right cells, at the right time. Enhancers are also the genomic sequences that encode the incredible diversity of cell types in the brain and enable the brain to turn genes on in response to new experiences. New technology enables enhancers to be found and manipulated. The study of enhancers promises to inform our understanding of brain development and function. The application of enhancer technology holds promise in accelerating basic neuroscience research and enabling gene therapies to be targeted to specific cell types in the brain.
在整个基因组中散布着数百万个称为转录增强子的调控序列，它们在正确的细胞、正确的时间激活基因启动子。增强子赋予大脑令人难以置信的细胞类型多样性，还能将神经活动转化为基因诱导。得益于基因组技术的快速发展，现在能够快速识别数千个增强子，大规模测试它们的转录功能，并通过基因组编辑研究它们的神经生物学功能。增强子也有望成为神经科学领域一个巨大的技术机遇，提供无需转基因即可进行细胞类型特异性基因标记和操纵的潜力。本综述以及同期举办的2015年神经科学学会小型研讨会的目的是强调利用新兴基因组技术探究神经系统中增强子功能的情况。
转录增强子在正确的细胞、正确的时间开启基因。增强子也是编码大脑中令人难以置信的细胞类型多样性的基因组序列，使大脑能够根据新的经历开启基因。新技术使增强子能够被发现和操纵。对增强子的研究有望增进我们对大脑发育和功能的理解。增强子技术的应用有望加速基础神经科学研究，并使基因疗法能够靶向大脑中的特定细胞类型。
