School of Life Science, Hubei Normal University, Huangshi 435002, Hubei, China.
National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Biochem Soc Trans. 2022 Dec 16;50(6):1809-1822. doi: 10.1042/BST20220763.
In eukaryotic cells, genomic DNA is hierarchically compacted by histones into chromatin, which is initially assembled by the nucleosome and further folded into orderly and flexible structures that include chromatin fiber, chromatin looping, topologically associated domains (TADs), chromosome compartments, and chromosome territories. These distinct structures and motifs build the three-dimensional (3D) genome architecture, which precisely controls spatial and temporal gene expression in the nucleus. Given that each type of cell is characterized by its own unique gene expression profile, the state of high-order chromatin plays an essential role in the cell fate decision. Accumulating evidence suggests that the plasticity of high-order chromatin is closely associated with stem cell fate. In this review, we summarize the biological roles of the state of high-order chromatin in embryogenesis, stem cell differentiation, the maintenance of stem cell identity, and somatic cell reprogramming. In addition, we highlight the roles of epigenetic factors and pioneer transcription factors (TFs) involved in regulating the state of high-order chromatin during the determination of stem cell fate and discuss how H3K9me3-heterochromatin restricts stem cell fate. In summary, we review the most recent progress in research on the regulatory functions of high-order chromatin dynamics in the determination and maintenance of stem cell fate.
在真核细胞中，基因组 DNA 被组蛋白分层压缩成染色质，染色质最初由核小体组装，并进一步折叠成有序且灵活的结构，包括染色质纤维、染色质环、拓扑关联域 (TAD)、染色质区室和染色体区室。这些不同的结构和基序构建了三维 (3D) 基因组结构，精确控制核内空间和时间基因表达。鉴于每种类型的细胞都具有其独特的基因表达谱，高级染色质的状态在细胞命运决定中起着至关重要的作用。越来越多的证据表明，高级染色质的可塑性与干细胞命运密切相关。在这篇综述中，我们总结了高级染色质状态在胚胎发生、干细胞分化、干细胞身份维持和体细胞重编程中的生物学作用。此外，我们强调了参与调节干细胞命运决定中高级染色质状态的表观遗传因子和先驱转录因子 (TF) 的作用，并讨论了 H3K9me3-异染色质如何限制干细胞命运。总之，我们综述了关于高级染色质动力学在干细胞命运决定和维持中的调控功能的最新研究进展。
