Signal Transduction and Targeted Therapy ( IF 40.8 ) Pub Date : 2024-12-04 , DOI: 10.1038/s41392-024-02030-9 Yang Chen, Rui Liang, Yong Li, Lingli Jiang, Di Ma, Qing Luo, Guanbin Song
The dynamic regulation of chromatin accessibility is one of the prominent characteristics of eukaryotic genome. The inaccessible regions are mainly located in heterochromatin, which is multilevel compressed and access restricted. The remaining accessible loci are generally located in the euchromatin, which have less nucleosome occupancy and higher regulatory activity. The opening of chromatin is the most important prerequisite for DNA transcription, replication, and damage repair, which is regulated by genetic, epigenetic, environmental, and other factors, playing a vital role in multiple biological progresses. Currently, based on the susceptibility difference of occupied or free DNA to enzymatic cleavage, solubility, methylation, and transposition, there are many methods to detect chromatin accessibility both in bulk and single-cell level. Through combining with high-throughput sequencing, the genome-wide chromatin accessibility landscape of many tissues and cells types also have been constructed. The chromatin accessibility feature is distinct in different tissues and biological states. Research on the regulation network of chromatin accessibility is crucial for uncovering the secret of various biological processes. In this review, we comprehensively introduced the major functions and mechanisms of chromatin accessibility variation in different physiological and pathological processes, meanwhile, the targeted therapies based on chromatin dynamics regulation are also summarized.
中文翻译:
染色质可及性:生物学功能、分子机制和治疗应用
染色质可及性的动态调控是真核基因组的突出特征之一。不可接近的区域主要位于异染色质中,异染色质是多级压缩且访问受限的。其余可接近的基因座通常位于常染色质中,其核小体占有率较低,调节活性较高。染色质的开放是 DNA 转录、复制和损伤修复的最重要前提,受遗传、表观遗传、环境和其他因素的调控,在多种生物进程中起着至关重要的作用。目前,基于占据或游离 DNA 对酶切割、溶解度、甲基化和转座的易感性差异,有许多方法可以检测大量和单细胞水平的染色质可及性。通过与高通量测序相结合,还构建了许多组织和细胞类型的全基因组染色质可及性景观。染色质可及性特征在不同的组织和生物状态中是不同的。对染色质可及性的调控网络的研究对于揭示各种生物过程的秘密至关重要。本文全面介绍了染色质可及性变异在不同生理和病理过程中的主要功能和机制,同时总结了基于染色质动力学调控的靶向治疗。