3D genome organization in the central nervous system,implications for neuropsychological disorders

Chromosomes in eukaryotic cell nuclei are highly compacted and finely organized into hierarchical threedimensional(3 D) configuration. In recent years, scientists have gained deeper understandings of 3 D genome structures and revealed novel evidence linking 3 D genome organization to various important cell events on the molecular level. Most importantly, alteration of 3 D genome architecture has emerged as an intriguing higher order mechanism that connects disease-related genetic variants in multiple heterogenous and polygenic neuropsychological disorders, delivering novel insights into the etiology. In this review, we provide a brief overview of the hierarchical structures of 3 D genome and two proposed regulatory models,loop extrusion and phase separation. We then focus on recent Hi-C data in the central nervous system and discuss 3 D genome alterations during normal brain development and in mature neurons. Most importantly,we make a comprehensive review on current knowledge and discuss the role of 3 D genome in multiple neuropsychological disorders, including schizophrenia, repeat expansion disorders, 22 q11 deletion syndrome, and others.