Biosciences Institute, The Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, U.K.
Biochem Soc Trans. 2021 Dec 17;49(6):2483-2493. doi: 10.1042/BST20200454.
Transcription is regulated and mediated by multiprotein complexes in a chromatin context. Transcription causes changes in DNA topology which is modulated by DNA topoisomerases, enzymes that catalyse changes in DNA topology via transient breaking and re-joining of one or both strands of the phosphodiester backbone. Mammals have six DNA topoisomerases, this review focuses on one, DNA topoisomerase II beta (TOP2B). In the absence of TOP2B transcription of many developmentally regulated genes is altered. Long genes seem particularly susceptible to the lack of TOP2B. Biochemical studies of the role of TOP2B in transcription regulated by ligands such as nuclear hormones, growth factors and insulin has revealed PARP1 associated with TOP2B and also PRKDC, XRCC5 and XRCC6. Analysis of publicly available databases of protein interactions confirms these interactions and illustrates interactions with other key transcriptional regulators including TRIM28. TOP2B has been shown to interact with proteins involved in chromosome organisation including CTCF and RAD21. Comparison of publicly available Chip-seq datasets reveals the location at which these proteins interact with genes. The availability of resources such as large datasets of protein-protein interactions, e.g. BioGrid and IntAct and protein-DNA interactions such as Chip-seq in GEO enables scientists to extend models and propose new hypotheses.
转录是在染色质环境中由多蛋白复合物调控和介导的。转录导致 DNA 拓扑结构的变化,而 DNA 拓扑异构酶则对其进行调节,该酶通过磷酸二酯骨架的一条或两条链的短暂断裂和重新连接来催化 DNA 拓扑结构的变化。哺乳动物有六种 DNA 拓扑异构酶,本综述重点介绍其中一种,即 DNA 拓扑异构酶 IIβ(TOP2B)。在缺乏 TOP2B 的情况下,许多发育调节基因的转录会发生改变。长基因似乎特别容易受到缺乏 TOP2B 的影响。对 TOP2B 在核激素、生长因子和胰岛素等配体调节的转录中的作用的生化研究揭示了与 TOP2B 相关的 PARP1,以及 PRKDC、XRCC5 和 XRCC6。对公开可用的蛋白质相互作用数据库的分析证实了这些相互作用,并说明了与其他关键转录调节剂的相互作用,包括 TRIM28。TOP2B 已被证明与参与染色体组织的蛋白质相互作用,包括 CTCF 和 RAD21。对公开可用的 Chip-seq 数据集的比较揭示了这些蛋白质与基因相互作用的位置。诸如 BioGrid 和 IntAct 等大型蛋白质-蛋白质相互作用数据集以及 GEO 中的 Chip-seq 等蛋白质-DNA 相互作用等资源的可用性使科学家能够扩展模型并提出新的假设。