Spiess Keeley, Won Hyejung
UNC Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA.
UNC Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
Curr Opin Genet Dev. 2020 Dec;65:53-60. doi: 10.1016/j.gde.2020.05.007. Epub 2020 Jun 18.
Although many regulatory elements in the non-coding genome are linked to brain development and disease, deciphering their function has been challenging due to the lack of a genomic toolbox. However, recent advances in high throughput sequencing techniques have allowed us to begin decoding its function, enhancing our understanding of the regulatory landscape that underpins human traits and brain disorders. Here, we review how the regulatory landscape of the human brain undergoes dynamic changes across neurodevelopment, different cell types, and human evolution. We then discuss how regulatory landscapes shed light onto the molecular basis of neuropsychiatric disorders and guide the development of specifically targeted molecular therapies. Finally, we offer some thoughts on how these discoveries might impact the direction of future studies.
尽管非编码基因组中的许多调控元件与大脑发育和疾病相关,但由于缺乏基因组工具箱,解读它们的功能一直具有挑战性。然而,高通量测序技术的最新进展使我们能够开始解码其功能,加深我们对支撑人类特征和脑部疾病的调控格局的理解。在这里,我们回顾了人类大脑的调控格局如何在神经发育、不同细胞类型和人类进化过程中发生动态变化。然后,我们讨论调控格局如何揭示神经精神疾病的分子基础,并指导特异性靶向分子疗法的开发。最后,我们对这些发现可能如何影响未来研究的方向提出了一些想法。