Chiariello Andrea M, Esposito Andrea, Annunziatella Carlo, Bianco Simona, Fiorillo Luca, Prisco Antonella, Nicodemi Mario
Dipartimento di Fisica, Università di Napoli Federico II, Naples, Italy.
Istituto Nazionale Di Fisica Nucleare Napoli (INFN), Complesso Universitario di Monte Sant'Angelo, Naples, Italy.
Front Neurosci. 2017 Oct 10;11:559. doi: 10.3389/fnins.2017.00559. eCollection 2017.
In the last decade, the developments of novel technologies, such as Hi-C or GAM methods, allowed to discover that chromosomes in the nucleus of mammalian cells have a complex spatial organization, encompassing the functional contacts between genes and regulators. In this work, we review recent progresses in chromosome modeling based on polymer physics to understand chromatin structure and folding mechanisms. As an example, we derive in mouse embryonic stem cells the full 3D structure of the locus, a genomic region that plays a key role in osteoblastic differentiation. Next, as an application to Neuroscience, we present the first 3D model for the mouse orthologoue of the Williams-Beuren syndrome human locus. Deletions and duplications of the region generate neurodevelopmental disorders with multi-system involvement and variable expressivity, and with autism. Understanding the impact of such mutations on the rewiring of the interactions of genes and regulators could be a new key to make sense of their related diseases, with potential applications in biomedicine.
在过去十年中，诸如Hi-C或GAM方法等新技术的发展，使人们发现哺乳动物细胞核中的染色体具有复杂的空间组织，包括基因与调控因子之间的功能联系。在这项工作中，我们回顾了基于聚合物物理学的染色体建模方面的最新进展，以了解染色质结构和折叠机制。例如，我们在小鼠胚胎干细胞中推导了一个在成骨细胞分化中起关键作用的基因组区域——位点的完整三维结构。接下来，作为神经科学的应用，我们展示了威廉姆斯-贝伦综合征人类位点的小鼠同源物的首个三维模型。该区域的缺失和重复会导致涉及多系统且具有可变表达性以及自闭症的神经发育障碍。了解此类突变对基因与调控因子相互作用重新连接的影响，可能是理解其相关疾病的新关键，在生物医学中具有潜在应用价值。
