Department of Neurology, Mass General Brigham, Boston, MA, U.S.A.
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI, U.S.A.
Biochem Soc Trans. 2023 Apr 26;51(2):703-713. doi: 10.1042/BST20220889.
The disruption of chromatin-regulating genes is associated with many neurocognitive syndromes. While most of these genes are ubiquitously expressed across various cell-types, many chromatin regulators act upon activity regulated genes (ARGs) that play central roles in synaptic development and plasticity. Recent literature suggests a link between ARG expression disruption in neurons with the human phenotypes observed in various neurocognitive syndromes. Advances in chromatin biology have demonstrated how chromatin structure, from nucleosome occupancy to higher-order structures such as topologically associated domains, impacts the kinetics of transcription. This review discusses the dynamics of these various levels of chromatin structure and their influence on the expression of ARGs.
染色质调节基因的紊乱与许多神经认知综合征有关。虽然这些基因大多数在各种细胞类型中广泛表达,但许多染色质调节剂作用于活性调节基因(ARGs),这些基因在突触发育和可塑性中起着核心作用。最近的文献表明,神经元中 ARG 表达的紊乱与各种神经认知综合征中观察到的人类表型之间存在联系。染色质生物学的进展表明,从核小体占据到拓扑相关结构等高级结构的染色质结构如何影响转录的动力学。这篇综述讨论了这些不同层次的染色质结构的动态及其对 ARG 表达的影响。