Center for Molecular and Cellular Biology, Skolkovo Institute of Science and Technology, Bolshoy Boulevard 30, Build.1, Moscow, 121205, Russia.
Research and Training Center on Bioinformatics, Institute for Information Transmission Problems (Kharkevich Institute) RAS, Bolshoy Karetny per. 19, Build.1, Moscow, 127051, Russia.
Epigenetics Chromatin. 2024 May 23;17(1):18. doi: 10.1186/s13072-024-00538-6.
The three-dimensional organization of the genome plays a central role in the regulation of cellular functions, particularly in the human brain. This review explores the intricacies of chromatin organization, highlighting the distinct structural patterns observed between neuronal and non-neuronal brain cells. We integrate findings from recent studies to elucidate the characteristics of various levels of chromatin organization, from differential compartmentalization and topologically associating domains (TADs) to chromatin loop formation. By defining the unique chromatin landscapes of neuronal and non-neuronal brain cells, these distinct structures contribute to the regulation of gene expression specific to each cell type. In particular, we discuss potential functional implications of unique neuronal chromatin organization characteristics, such as weaker compartmentalization, neuron-specific TAD boundaries enriched with active histone marks, and an increased number of chromatin loops. Additionally, we explore the role of Polycomb group (PcG) proteins in shaping cell-type-specific chromatin patterns. This review further emphasizes the impact of variations in chromatin architecture between neuronal and non-neuronal cells on brain development and the onset of neurological disorders. It highlights the need for further research to elucidate the details of chromatin organization in the human brain in order to unravel the complexities of brain function and the genetic mechanisms underlying neurological disorders. This research will help bridge a significant gap in our comprehension of the interplay between chromatin structure and cell functions.
基因组的三维组织在细胞功能的调控中起着核心作用，特别是在人类大脑中。本综述探讨了染色质组织的复杂性，强调了神经元和非神经元脑细胞之间观察到的不同结构模式。我们整合了最近研究的发现，阐明了各种层次的染色质组织的特征，从差异区室化和拓扑关联域（TADs）到染色质环形成。通过定义神经元和非神经元脑细胞独特的染色质景观，这些不同的结构有助于调节每种细胞类型特有的基因表达。特别是，我们讨论了独特的神经元染色质组织特征的潜在功能意义，例如较弱的区室化、富含活性组蛋白标记的神经元特异性 TAD 边界，以及更多的染色质环。此外，我们还探讨了 Polycomb 组（PcG）蛋白在塑造细胞类型特异性染色质模式中的作用。本综述进一步强调了神经元和非神经元细胞之间染色质结构差异对大脑发育和神经障碍发生的影响。它强调了需要进一步研究阐明人类大脑中染色质组织的细节，以揭示大脑功能和神经障碍背后遗传机制的复杂性。这项研究将有助于缩小我们对染色质结构与细胞功能相互作用理解的差距。
