Epigenetics and Sex Development Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Center for Molecular Medicine, Berlin, Germany.
Brief Funct Genomics. 2020 Mar 23;19(2):128-138. doi: 10.1093/bfgp/elz028.
A precise three-dimensional (3D) organization of chromatin is central to achieve the intricate transcriptional patterns that are required to form complex organisms. Growing evidence supports an important role of 3D chromatin architecture in development and delineates its alterations as prominent causes of disease. In this review, we discuss emerging concepts on the fundamental forces shaping genomes in space and on how their disruption can lead to pathogenic phenotypes. We describe the molecular mechanisms underlying a wide range of diseases, from the systemic effects of coding mutations on 3D architectural factors, to the more tissue-specific phenotypes resulting from genetic and epigenetic modifications at specific loci. Understanding the connection between the 3D organization of the genome and its underlying biological function will allow a better interpretation of human pathogenesis.
染色质的精确三维（3D）组织对于实现形成复杂生物体所需的复杂转录模式至关重要。越来越多的证据支持 3D 染色质结构在发育中的重要作用，并将其改变描述为疾病的主要原因。在这篇综述中，我们讨论了塑造基因组在空间中基本力的新兴概念，以及它们的破坏如何导致致病表型。我们描述了广泛疾病的分子机制，从编码突变对 3D 结构因子的系统影响，到特定基因座遗传和表观遗传修饰导致的更具组织特异性的表型。理解基因组的 3D 组织与其基础生物学功能之间的联系将有助于更好地解释人类发病机制。
