Duke University School of Medicine, Department of Neurobiology, Durham, NC 27710, USA.
Duke University School of Medicine, Department of Neurobiology, Durham, NC 27710, USA.
Curr Opin Neurobiol. 2024 Dec;89:102915. doi: 10.1016/j.conb.2024.102915. Epub 2024 Sep 14.
Epigenetic regulation of the genome is required for cell-type differentiation during organismal development and is especially important to generate the panoply of specialized cell types that comprise the brain. Here, we review how progressive changes in the chromatin landscape, both in neural progenitors and in postmitotic neurons, orchestrate the timing of gene expression programs that underlie first neurogenesis and then functional neuronal maturation. We discuss how disease-associated mutations in chromatin regulators can change brain composition by impairing the timing of neurogenesis. Further, we highlight studies that are beginning to show how chromatin modifications are integrated at the level of chromatin architecture to coordinate changing transcriptional programs across developmental including in postmitotic neurons.
基因组的表观遗传调控对于生物体发育过程中的细胞类型分化是必需的,对于产生构成大脑的各种特化细胞类型尤为重要。在这里,我们回顾了染色质景观在神经祖细胞和有丝分裂后神经元中的渐进变化如何协调基因表达程序的时间,这些程序是神经发生和随后的功能性神经元成熟的基础。我们讨论了染色质调节因子中的疾病相关突变如何通过破坏神经发生的时间来改变大脑组成。此外,我们强调了一些研究,这些研究开始表明染色质修饰如何在染色质结构水平上整合,以协调发育过程中包括有丝分裂后神经元在内的转录程序的变化。