Nucleic Acids Research最新文献

EBNA leader protein orchestrates chromatin architecture remodeling during Epstein-Barr virus-induced B cell transformation eb - na领导蛋白在eb病毒诱导的B细胞转化过程中协调染色质结构重塑

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-07-02 DOI: 10.1093/nar/gkaf629

Davide Maestri, Lisa B Caruso, Jana M Cable, Rachel Sklutuis, Sarah Preston-Alp, Robert E White, Micah A Luftig, Italo Tempera

{"title":"EBNA leader protein orchestrates chromatin architecture remodeling during Epstein-Barr virus-induced B cell transformation","authors":"Davide Maestri, Lisa B Caruso, Jana M Cable, Rachel Sklutuis, Sarah Preston-Alp, Robert E White, Micah A Luftig, Italo Tempera","doi":"10.1093/nar/gkaf629","DOIUrl":"https://doi.org/10.1093/nar/gkaf629","url":null,"abstract":"Epstein-Barr virus Nuclear Antigen Leader Protein (EBNA-LP) plays a pivotal role in the transformation of B cells by Epstein-Barr virus (EBV), functioning independently of EBNA2 to regulate chromatin architecture and gene expression. Our study reveals that EBNA-LP binds to chromatin regions distinct from EBNA2 and facilitates the formation of long-distance chromatin loops by interacting with the cellular factor YY1. This interaction reconfigures the three-dimensional structure of the host genome, enhancing the integrity of topologically associating domains (TADs) and promoting the interaction between enhancers and promoters within these domains. In EBV-infected B cells, EBNA-LP strengthens YY1-mediated chromatin loops within TADs, which helps maintain stable regulatory programs essential for B cell transformation. Notably, EBNA-LP is crucial for establishing EBV-induced enhancers, yet it is not required for their maintenance once formed. Additionally, our data suggest a compensatory increase in CTCF binding in the absence of EBNA-LP, leading to more promiscuous chromatin interactions between TADs and a reduced TAD insulation at their boundaries. These findings provide new insights into the molecular mechanisms by which EBV reshapes the host genome chromatin architecture to support B cell transformation and highlight potential therapeutic targets for disrupting EBV-driven oncogenesis.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"272 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel enzyme-based reduced representation method for DNA methylation profiling with low inputs 基于酶的低输入DNA甲基化谱简化表示新方法

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-06-30 DOI: 10.1093/nar/gkaf558

Qianli Liu, Kathryn A Helmin, Zachary D Dortzbach, Carla P Reyes Flores, Manuel A Torres Acosta, Jonathan K Gurkan, Anthony M Joudi, Nurbek Mambetsariev, Luisa Morales-Nebreda, Mengjia Kang, Luke Rasmussen, Xóchitl G Pérez-Leonor, Hiam Abdala-Valencia, Benjamin D Singer

{"title":"Novel enzyme-based reduced representation method for DNA methylation profiling with low inputs","authors":"Qianli Liu, Kathryn A Helmin, Zachary D Dortzbach, Carla P Reyes Flores, Manuel A Torres Acosta, Jonathan K Gurkan, Anthony M Joudi, Nurbek Mambetsariev, Luisa Morales-Nebreda, Mengjia Kang, Luke Rasmussen, Xóchitl G Pérez-Leonor, Hiam Abdala-Valencia, Benjamin D Singer","doi":"10.1093/nar/gkaf558","DOIUrl":"https://doi.org/10.1093/nar/gkaf558","url":null,"abstract":"Commonly used bisulfite-based procedures for DNA methylation sequencing can degrade DNA, worsening signal-to-noise ratios in samples with low DNA input. Enzymatic methylation sequencing (EM-seq) has been proposed as a less biased alternative for methylation profiling with greater genome coverage. Reduced representation approaches enrich samples for CpG-rich genomic regions, thereby enhancing throughput and cost effectiveness. We hypothesized that enzyme-based technology could be adapted for reduced representation methylation sequencing to enable DNA methylation profiling of low-input samples. We leveraged the well-established differences in methylation profile between mouse CD4+ T cell populations to compare the performance of our reduced representation EM-seq (RREM-seq) procedure against an established reduced representation bisulfite sequencing (RRBS) protocol. While the RRBS method failed to generate reliable DNA libraries when using &lt;2 ng of DNA, the RREM-seq method successfully generated reliable DNA libraries from 1–25 ng of mouse and human DNA. Low-input (≤2-ng) RREM-seq libraries demonstrated superior regulatory genomic element coverage compared with RRBS libraries with &gt;10-fold higher DNA input. RREM-seq also successfully detected lineage-defining methylation differences between alveolar conventional T and regulatory T cells obtained from patients with severe SARS-CoV-2 pneumonia. Our RREM-seq method enables single-nucleotide resolution methylation profiling using low-input samples, including from clinical sources.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"9 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144516002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural heterogeneity and dynamics in the apical stem loop of s2m from SARS-CoV-2 Delta by an integrative NMR spectroscopy and MD simulation approach 基于核磁共振波谱和MD模拟的SARS-CoV-2三角洲s2m根茎环结构异质性和动力学研究

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-06-30 DOI: 10.1093/nar/gkaf552

Maria A Wirtz Martin, Joseph A Makowski, Tobias Matzel, Adam H Kensinger, Alexander Herr, Christian Richter, Hendrik R A Jonker, Anna Wacker, Jeffrey D Evanseck, Harald Schwalbe

{"title":"Structural heterogeneity and dynamics in the apical stem loop of s2m from SARS-CoV-2 Delta by an integrative NMR spectroscopy and MD simulation approach","authors":"Maria A Wirtz Martin, Joseph A Makowski, Tobias Matzel, Adam H Kensinger, Alexander Herr, Christian Richter, Hendrik R A Jonker, Anna Wacker, Jeffrey D Evanseck, Harald Schwalbe","doi":"10.1093/nar/gkaf552","DOIUrl":"https://doi.org/10.1093/nar/gkaf552","url":null,"abstract":"In structured RNAs, helical elements are often capped by apical loops that are integral structural elements, ranging from 3 to &gt;20 nts of size on average, and display a highly heterogeneous energy landscape profile, rendering structural characterization particularly challenging. We here provide a characterization of the SARS-CoV-2 Delta s2m element containing a highly dynamic nonaloop using an integrative approach of nuclear magnetic resonance spectroscopy (NMR), small angle X-ray scattering (SAXS), and molecular dynamics simulations (MD). We further explored the conformational space in the s2m nonaloop and its transient closing 5′-G-U-3′ base pair by MD simulations weighted by experimental NMR observables, leading to a comprehensive representation of the s2m nonaloop motif. Our deconvolution of the ensemble into conformations and dynamics provides a basis for future ensemble-functional characterization of RNA structures featuring dynamic motifs.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"25 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144516093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification and correction of time-series transcriptomic anomalies 时间序列转录组异常的识别和校正

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-06-30 DOI: 10.1093/nar/gkaf524

Sophia A Campione, Christina M Kelliher, Cullen Roth, Chun Yi Cho, Anastasia Deckard, Francis Motta, Steven B Haase

{"title":"Identification and correction of time-series transcriptomic anomalies","authors":"Sophia A Campione, Christina M Kelliher, Cullen Roth, Chun Yi Cho, Anastasia Deckard, Francis Motta, Steven B Haase","doi":"10.1093/nar/gkaf524","DOIUrl":"https://doi.org/10.1093/nar/gkaf524","url":null,"abstract":"Transcriptomic analyses performed in time series have uncovered many important insights into dynamic biological processes such as circadian rhythms, cellular developmental cycles, and the cell cycle. Some of these studies have revealed transcriptomic artifacts (STRIPEs), characterized by substantial changes in transcript levels across the transcriptome between a time point and its temporal neighbors. These changes are unlikely to reflect underlying biology as the magnitude of the change is too large to occur within the time interval and because every gene in the time point exhibits a substantial change. Furthermore, STRIPEs occur across species exhibiting different biology, do not occur in the same phase across replicate time-series experiments, and can vary between technical replicates of a single time point. Here, we demonstrate STRIPEs in five time-series transcriptomic datasets across different species, biological processes, and timescales. We describe a computational method to detect STRIPEs in time series using the Kolmogorov–Smirnov statistical test, allowing for unbiased, user-friendly detection of STRIPEs. Finally, we present three methods for STRIPE correction and demonstrate their efficacy. Using periodicity analysis to identify periodic genes, we find nearly 600 genes changed in periodicity labeling following successful STRIPE correction, indicating the large impact of STRIPE removal on downstream analysis.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"64 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144521055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Twisting tetraplex DNA: A strand dynamics regulating i-motif function in diverse molecular crowding environments 扭曲四体DNA：在不同分子拥挤环境中调节i-motif功能的链动力学

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-06-30 DOI: 10.1093/nar/gkaf500

Shuntaro Takahashi, Saptarshi Ghosh, Marko Trajkovski, Tatsuya Ohyama, Janez Plavec, Naoki Sugimoto

{"title":"Twisting tetraplex DNA: A strand dynamics regulating i-motif function in diverse molecular crowding environments","authors":"Shuntaro Takahashi, Saptarshi Ghosh, Marko Trajkovski, Tatsuya Ohyama, Janez Plavec, Naoki Sugimoto","doi":"10.1093/nar/gkaf500","DOIUrl":"https://doi.org/10.1093/nar/gkaf500","url":null,"abstract":"Intercalated motif (i-motif) tetraplex DNA plays a crucial role in gene expression and diseases. However, due to the limited number of i-motif binding proteins in human cells, the chemical mechanisms regulating i-motifs within cell remain currently unknown. Thus, molecular environment should have a main factor to control i-motif formation and functions in cells. Here, we systematically investigated the stability and functions of i-motif DNAs by using various polyethylene glycols (PEGs) and oligoethylene glycols (OEGs) that mimicked diverse cellular crowding environments. We found that the human telomere i-motif was significantly stabilized by PEGs and OEGs having six or more ethylene glycol units, whereas it was destabilized by those having less than six units. As these stabilization effects coincided with the drastic changes in hypochromicity by i-motif helixes, we quantitatively validated these effects through changes in solution properties and by assessing the twisting of the tetraplex structure using nuclear magnetic resonance (NMR) and molecular dynamics simulations. Furthermore, cosolute-induced twisting dynamics controlled by different cosolutes changed the activation energy barrier of replication by a twofold magnitude along the i-motif-forming DNAs. Our findings indicate that regulatory mechanisms underlying the biological roles of i-motifs across different cellular phases may exist by molecular environments.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"47 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tiny but multi-stable: four distinct conformational states govern the ligand-free state of the preQ1 riboswitch from a thermophilic bacterium 微小但多稳定：嗜热细菌的preQ1核糖开关的无配体状态由四种不同的构象状态控制

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-06-30 DOI: 10.1093/nar/gkaf560

Stefanie Rückriegel, Konstantinos Stamatakis, Josef Wachtveitl, Boris Fürtig

{"title":"Tiny but multi-stable: four distinct conformational states govern the ligand-free state of the preQ1 riboswitch from a thermophilic bacterium","authors":"Stefanie Rückriegel, Konstantinos Stamatakis, Josef Wachtveitl, Boris Fürtig","doi":"10.1093/nar/gkaf560","DOIUrl":"https://doi.org/10.1093/nar/gkaf560","url":null,"abstract":"Translational riboswitches are bacterial gene regulatory elements located in the 5′-untranslated region of mRNAs. They operate through a conformational refolding reaction that is triggered by a change in concentration of a modulating small molecule ligand. The initially model posited that the two functional states, the ligand-bound and ligand-free state, would only populate two stable conformations. However, the subsequent discoveries of multiple conformations for the apo- and holo-states of riboswitches have rendered this model obsolete. Concomitantly, a comprehensive account of the conformational multistability of riboswitches has remained elusive. In this study, we demonstrate that even the smallest naturally occurring translational riboswitch, the preQ1-sensing riboswitch from Thermoanaerobacter tengcongensis, adopts four distinct and structurally different conformations in the absence of ligand. This is in contrast to structures determined by X-ray crystallography, which reveal only minor deviations between the ligand-free and ligand-bound states. Utilizing NMR-spectroscopic analysis, we characterize the structurally heterogeneous apo-state and depict four distinct conformations that demonstrate varying temperature stabilities. Upon ligand-binding, the folding pathway undergoes kinetic partitioning, thereby enabling regulatory plasticity to integrate multiple environmental inputs for riboswitch-based gene regulation.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"26 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The quantitative impact of 3′UTRs on gene expression 3'UTRs对基因表达的定量影响

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-06-30 DOI: 10.1093/nar/gkaf568

Jessica D West, Hannah J Smith, Luyen Tien Vu, Elizabeth A Fogarty, Kenneth A Matreyek, Douglas M Fowler, Andrew Grimson

{"title":"The quantitative impact of 3′UTRs on gene expression","authors":"Jessica D West, Hannah J Smith, Luyen Tien Vu, Elizabeth A Fogarty, Kenneth A Matreyek, Douglas M Fowler, Andrew Grimson","doi":"10.1093/nar/gkaf568","DOIUrl":"https://doi.org/10.1093/nar/gkaf568","url":null,"abstract":"Control of gene expression is fundamental to biology, and post-transcriptional regulation is an important component of this process. In mammals, the 3′UTR in particular serves as a major source of regulatory information within the transcript. Here we developed an accurate massively parallel reporter assay (MPRA) system to evaluate the impact of &gt;1400 full-length human 3′UTRs on RNA abundance, stability, translational regulation, and total protein output. We demonstrated that our MPRA is consistent with regulation of the corresponding endogenous transcripts. We used the MPRA datasets to model the relative contributions of RNA abundance and translational efficiency toward total 3′UTR-mediated regulation, revealing an unexpectedly large role for 3′UTR-specified translational control, and providing additional evidence that much of 3′UTR-encoded regulation is mediated by concerted regulation of translation plus decay. We observed relationships between GC content and 3′UTR length and different modes of regulation, and identified sequence motifs corresponding to regulatory RNA-binding proteins associated with mediating 3′UTR-dependent gene expression. We compared regulation from &gt;1400 3′UTRs under control of two dissimilar promoters, which revealed promoter-associated differences in post-transcriptional regulation for certain 3′UTRs. Together, this dataset represents a comprehensive characterization of 3′UTR-mediated quantitative regulation.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"63 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144516004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ERH regulates type II interferon immune signaling through post-transcriptional regulation of JAK2 mRNA ERH通过转录后调控JAK2 mRNA调控II型干扰素免疫信号

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-06-30 DOI: 10.1093/nar/gkaf545

Adrian Soderholm, Milica Vunjak, Melanie de Almeida, Niko Popitsch, Nadezda Podvalnaya, Pablo Araguas-Rodriguez, Sara Scinicariello, Emily Nischwitz, Falk Butter, René F Ketting, Stefan L Ameres, Michaela Müller-McNicoll, Johannes Zuber, Gijs A Versteeg

{"title":"ERH regulates type II interferon immune signaling through post-transcriptional regulation of JAK2 mRNA","authors":"Adrian Soderholm, Milica Vunjak, Melanie de Almeida, Niko Popitsch, Nadezda Podvalnaya, Pablo Araguas-Rodriguez, Sara Scinicariello, Emily Nischwitz, Falk Butter, René F Ketting, Stefan L Ameres, Michaela Müller-McNicoll, Johannes Zuber, Gijs A Versteeg","doi":"10.1093/nar/gkaf545","DOIUrl":"https://doi.org/10.1093/nar/gkaf545","url":null,"abstract":"Type II interferon (IFNγ) signaling is essential for innate immunity and critical for effective immunological checkpoint blockade in cancer immunotherapy. Genetic screen identification of post-transcriptional regulators of this pathway has been challenging since such factors are often essential for cell viability. Here, we utilize our inducible CRISPR/Cas9 approach to screen for key post-transcriptional regulators of IFNγ signaling, and in this way, we identify ERH and the ERH-associated splicing and RNA export factors MAGOH, SRSF1, and ALYREF. Loss of these factors impairs post-transcriptional mRNA maturation of JAK2, a crucial kinase for IFNγ signaling, resulting in abrogated JAK2 protein levels and diminished IFNγ signaling. Further analysis highlights a critical role for ERH in preventing intron retention in AU-rich regions in specific transcripts, such as JAK2. This regulation is markedly different from previously described retention of GC-rich introns. Overall, these findings reveal that post-transcriptional JAK2 processing is a critical rate-limiting step for the IFNγ-driven innate immune response.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"63 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144516110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Extrusion fountains are restricted by WAPL-dependent cohesin release and CTCF barriers 挤压喷泉受到依赖于wapl的黏结物释放和CTCF屏障的限制

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-06-30 DOI: 10.1093/nar/gkaf549

Ning Qing Liu, Mikhail Magnitov, Marijne M G A Schijns, Tom van Schaik, Hans Teunissen, Bas van Steensel, Elzo de Wit

{"title":"Extrusion fountains are restricted by WAPL-dependent cohesin release and CTCF barriers","authors":"Ning Qing Liu, Mikhail Magnitov, Marijne M G A Schijns, Tom van Schaik, Hans Teunissen, Bas van Steensel, Elzo de Wit","doi":"10.1093/nar/gkaf549","DOIUrl":"https://doi.org/10.1093/nar/gkaf549","url":null,"abstract":"Interphase chromosomes are mainly shaped by loop extrusion and compartmentalisation mechanisms. However, their temporal component and cause-effect relationships remain largely unknown. In this study, we use acute degradation of WAPL, CTCF and cohesin in mouse embryonic stem cells to investigate the dynamics of loop extrusion and its relationship to compartmentalisation. Stabilisation of cohesin on chromatin by depletion of WAPL results in the formation of extended loops and promotes looping between non-convergent CTCF sites. Loss of WAPL also results in a rapid decrease in compartmentalisation, which is reversed by subsequent removal of cohesin, directly demonstrating the opposite role of extrusion on compartmentalisation. Using combined depletion of WAPL and CTCF, we identify fountains, a feature of chromosome organisation that emanates from enhancer regions and exhibits strong cohesin binding. Fountains form rapidly after mitosis and early in mammalian development. Cohesin depletion confirms that fountains are cohesin dependent, and their disruption leads to the downregulation of fountain-proximal genes, suggesting a role in gene regulation. Taken together, by exploiting the temporal precision of acute protein depletion, our study reveals fountains as an extrusion-mediated, fast-forming feature of 3D genome organisation.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"36 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144516000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Significance of the CTP-binding motif for the interactions of S. coelicolor ParB with DNA, chromosome segregation, and sporogenic hyphal growth ctp结合基序在S. coelicolor ParB与DNA、染色体分离和孢子生菌丝生长的相互作用中的意义

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-06-30 DOI: 10.1093/nar/gkaf623

Justyna Szymczak, Agnieszka Strzałka, Dominik Bania, Dagmara Jakimowicz, Marcin Jan Szafran

{"title":"Significance of the CTP-binding motif for the interactions of S. coelicolor ParB with DNA, chromosome segregation, and sporogenic hyphal growth","authors":"Justyna Szymczak, Agnieszka Strzałka, Dominik Bania, Dagmara Jakimowicz, Marcin Jan Szafran","doi":"10.1093/nar/gkaf623","DOIUrl":"https://doi.org/10.1093/nar/gkaf623","url":null,"abstract":"The segregation of bacterial chromosomes is widely mediated by partitioning proteins (ParAB). While ParB binds DNA specifically by recognizing short, palindromic sequences known as parS sites, ParA utilizes its ATPase activity to generate the force to translocate ParB–DNA nucleoprotein complexes (segrosomes). The assembly of the segrosome requires the association of ParB with parS, followed by nonspecific spread of the protein along the DNA. To spread on DNA, the ParB dimer must entrap the parS site within the complex, a process triggered by CTP binding to the conserved GERR amino acid motif. In Streptomyces, a genus of soil-dwelling, multigenomic bacteria that have a complex life cycle, ParB-dependent chromosome partitioning is initiated during the growth of sporogenic hyphae. However, the molecular mechanisms underlying segrosome formation in Streptomyces and their ability to coordinate with sporogenic development remain incompletely understood. In this study, we advance the understanding of chromosome segregation in bacteria by exploring the effects of CTP binding and hydrolysis on the formation of the partitioning complex in Streptomyces coelicolor. Here, via in vitro approaches, we demonstrate that a conserved GERR motif is essential for CTP binding and hydrolysis by S. coelicolor ParB. Moreover, the motif is crucial for CTP-dependent ParB accumulation on DNA. Using mutant strains, we show the significance of the GERR motif for segrosome complex assembly. Additionally, we provide data showing that the CTP-binding motif contributes to the regulation of the growth of sporogenic cells. Overall, we show that CTP-dependent segrosome assembly impacts the development of S. coelicolor sporogenic cells.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"27 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144516001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0