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有关，但由于缺乏基因组工具箱，破译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，增强我们对支撑人类特征和大脑疾病的监管格局的理解。在这里，我们回顾了人类大脑的调节景观如何在神经发育、不同细胞类型和人类进化过程中发生动态变化。然后我们讨论监管环境如何阐明神经精神疾病的分子基础并指导特定靶向分子疗法的开发。最后，我们就这些发现如何影响未来研究的方向提出了一些想法。