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来自枯草芽孢杆菌的Rok:连接基因组结构与转录调控

Rok from B. subtilis: Bridging genome structure and transcription regulation.

作者信息

Erkelens Amanda M, van Erp Bert, Meijer Wilfried J J, Dame Remus T

机构信息

Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands.

Centre for Microbial Cell Biology, Leiden University, Leiden, the Netherlands.

出版信息

Mol Microbiol. 2025 Feb;123(2):109-123. doi: 10.1111/mmi.15250. Epub 2024 Mar 21.

DOI:10.1111/mmi.15250
PMID:38511404
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11841835/
Abstract

Bacterial genomes are folded and organized into compact yet dynamic structures, called nucleoids. Nucleoid orchestration involves many factors at multiple length scales, such as nucleoid-associated proteins and liquid-liquid phase separation, and has to be compatible with replication and transcription. Possibly, genome organization plays an intrinsic role in transcription regulation, in addition to classical transcription factors. In this review, we provide arguments supporting this view using the Gram-positive bacterium Bacillus subtilis as a model. Proteins BsSMC, HBsu and Rok all impact the structure of the B. subtilis chromosome. Particularly for Rok, there is compelling evidence that it combines its structural function with a role as global gene regulator. Many studies describe either function of Rok, but rarely both are addressed at the same time. Here, we review both sides of the coin and integrate them into one model. Rok forms unusually stable DNA-DNA bridges and this ability likely underlies its repressive effect on transcription by either preventing RNA polymerase from binding to DNA or trapping it inside DNA loops. Partner proteins are needed to change or relieve Rok-mediated gene repression. Lastly, we investigate which features characterize H-NS-like proteins, a family that, at present, lacks a clear definition.

摘要

细菌基因组被折叠并组织成紧凑而动态的结构,称为类核。类核调控涉及多个长度尺度上的许多因素,如类核相关蛋白和液-液相分离,并且必须与复制和转录相兼容。除了经典转录因子外,基因组组织可能在转录调控中发挥内在作用。在本综述中,我们以革兰氏阳性细菌枯草芽孢杆菌为模型,提供支持这一观点的论据。蛋白质BsSMC、HBsu和Rok都会影响枯草芽孢杆菌染色体的结构。特别是对于Rok,有令人信服的证据表明它将其结构功能与作为全局基因调节因子的作用结合在一起。许多研究只描述了Rok的一种功能,但很少同时涉及这两种功能。在这里,我们审视了问题的两面,并将它们整合到一个模型中。Rok形成异常稳定的DNA-DNA桥,这种能力可能是其对转录产生抑制作用的基础,其作用方式要么是阻止RNA聚合酶与DNA结合,要么是将其困在DNA环内。需要伴侣蛋白来改变或解除Rok介导的基因抑制。最后,我们研究了H-NS样蛋白的特征,这是一个目前缺乏明确定义的家族。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a278/11841835/8f1e24355727/MMI-123-109-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a278/11841835/8f1e24355727/MMI-123-109-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a278/11841835/8f1e24355727/MMI-123-109-g001.jpg

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Nat Commun. 2024 Mar 28;15(1):2737. doi: 10.1038/s41467-024-47094-x.
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c-di-GMP inhibits the DNA binding activity of H-NS in Salmonella.c-di-GMP 抑制沙门氏菌中 H-NS 的 DNA 结合活性。
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Nucleic Acids Res. 2024 Dec 11;52(22):13945-13963. doi: 10.1093/nar/gkae1104.
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MucR acts as an H-NS-like protein to silence virulence genes and structure the nucleoid.MucR 作为一种类似于 H-NS 的蛋白,可使毒力基因沉默并对核基质进行结构重塑。
mBio. 2023 Dec 19;14(6):e0220123. doi: 10.1128/mbio.02201-23. Epub 2023 Oct 17.
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TADs: Dynamic structures to create stable regulatory functions.TADs:动态结构创造稳定的调控功能。
Curr Opin Struct Biol. 2023 Aug;81:102622. doi: 10.1016/j.sbi.2023.102622. Epub 2023 Jun 9.
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Looping the Genome with SMC Complexes.SMC 复合物的基因组环化。
Annu Rev Biochem. 2023 Jun 20;92:15-41. doi: 10.1146/annurev-biochem-032620-110506. Epub 2023 May 3.
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The bacterial nucleoid-associated proteins, HU and Dps, condense DNA into context-dependent biphasic or multiphasic complex coacervates.细菌核相关蛋白 HU 和 Dps 将 DNA 凝聚成与环境相关的两相或多相复合凝聚物。
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A new role for monomeric ParA/Soj in chromosome dynamics in Bacillus subtilis.单体 ParA/Soj 在枯草芽孢杆菌染色体动力学中的新作用。
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