gene transcription

基因转录
  • 文章类型: Journal Article
    ATP依赖性染色质重塑剂在利用ATP水解的能量修饰染色质构型中起着至关重要的作用。他们参与了各种过程,包括转录,DNA复制,保持基因组的稳定性。这些重塑重塑分子通常在真核生物中形成多亚基染色质重塑复合物。在植物中,染色质重塑复合物在调节植物发育和胁迫反应方面具有多种功能。最近的研究对植物染色质重塑复合物进行了广泛的研究。本文综述了植物染色质重塑复合物的分类和组成的最新进展,复合物中的蛋白质-蛋白质相互作用,它们对染色质构型的影响,以及它们与染色质修饰和转录因子的相互作用。
    ATP-dependent chromatin remodelers play a crucial role in modifying chromatin configuration by utilizing the energy of ATP hydrolysis. They are involved in various processes, including transcription, DNA replication, and maintaining genome stability. These remodeling remodelers usually form multi-subunit chromatin remodeling complexes in eukaryotes. In plants, chromatin remodeling complexes have diverse functions in regulating plant development and stress response. Recent studies have conducted extensive research on plant chromatin remodeling complexes. This review focuses on recent advances in the classification and composition of plant chromatin remodeling complexes, the protein-protein interactions within the complexes, their impact on chromatin configuration, and their interactions with chromatin modifications and transcription factors.
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  • 文章类型: Journal Article
    转谷氨酰胺酶2(TGM2)是一种具有良好特征的调节多种癌症进展的因子,由于它的多功能活动和它所参与的无处不在的信号通路。作为转谷氨酰胺酶家族的一员,TGM2催化蛋白质翻译后修饰(PTM),包括单氨基化,酰胺水解,交联,等。,通过含谷氨酰胺的变体蛋白质底物的转酰胺化。最近的发现表明组蛋白是TGM2底物的重要类别,因此确定组蛋白单氨基化是一种新兴的表观遗传标记,在癌细胞中高度富集,具有显著的基因转录调控功能。在这次审查中,我们将总结TGM2介导的组蛋白单氨基化及其在癌症中的作用的最新进展,并讨论关键的研究方法,以更好地理解这种独特的表观遗传标记,从而揭示了TGM2作为癌症治疗中的药物靶标的治疗潜力。
    Transglutaminase 2 (TGM2) has been known as a well-characterized factor regulating the progression of multiple types of cancer, due to its multifunctional activities and the ubiquitous signaling pathways it is involved in. As a member of the transglutaminase family, TGM2 catalyzes protein post-translational modifications (PTMs), including monoaminylation, amide hydrolysis, crosslinking, etc., through the transamidation of variant glutamine-containing protein substrates. Recent discoveries revealed histone as an important category of TGM2 substrates, thus identifying histone monoaminylation as an emerging epigenetic mark, which is highly enriched in cancer cells and possesses significant regulatory functions of gene transcription. In this review, we will summarize recent advances in TGM2-mediated histone monoaminylation as well as its role in cancer and discuss the key research methodologies to better understand this unique epigenetic mark, thereby shedding light on the therapeutic potential of TGM2 as a druggable target in cancer treatment.
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  • 文章类型: Journal Article
    Eaf6蛋白,酵母和人类MOZ/MORF复合物中NuA4和NuA3复合物的保守成分,在转录激活中起着至关重要的作用,基因调控,和细胞周期控制。尽管它在其他生物体中具有重要意义,Eaf6在昆虫病原真菌(EPF)中的功能作用仍未被探索。这里,我们研究了Eaf6同源物在昆虫病原真菌球孢白僵菌中的功能。我们证明BbEaf6主要位于细胞核中,与其他真菌类似。BbEaf6的删除导致延迟的分生孢子,分生孢子产量降低,并改变了分生孢子的性质。转录组学分析显示,ΔBbEaf6突变体中涉及无性发育和细胞周期进程的基因失调。此外,ΔBbEaf6突变体对各种胁迫的耐受性降低,包括离子应力,细胞壁扰动,和DNA损伤压力。值得注意的是,ΔBbEaf6突变体在昆虫生物测定中显示出减弱的毒力,伴随着与角质层渗透和血球感染相关的基因失调。总的来说,我们的研究阐明了BbEaf6在应激反应中的多方面作用,发展,和B.bassiana的毒力,为控制真菌发病机理的分子机制和害虫管理策略的潜在目标提供有价值的见解。
    The Eaf6 protein, a conserved component of the NuA4 and NuA3 complexes in yeast and MOZ/MORF complexes in humans, plays crucial roles in transcriptional activation, gene regulation, and cell cycle control. Despite its significance in other organisms, the functional role of Eaf6 in entomopathogenic fungi (EPF) remained unexplored. Here, we investigate the function of BbEaf6, the Eaf6 homolog in the entomopathogenic fungus Beauveria bassiana. We demonstrate that BbEaf6 is predominantly localized in nuclei, similar to its counterpart in other fungi. Deletion of BbEaf6 resulted in delayed conidiation, reduced conidial yield, and altered conidial properties. Transcriptomic analysis revealed dysregulation of the genes involved in asexual development and cell cycle progression in the ΔBbEaf6 mutant. Furthermore, the ΔBbEaf6 mutant exhibited decreased tolerance to various stresses, including ionic stress, cell wall perturbation, and DNA damage stress. Notably, the ΔBbEaf6 mutant displayed attenuated virulence in insect bioassays, accompanied by dysregulation of genes associated with cuticle penetration and haemocoel infection. Overall, our study elucidates the multifaceted role of BbEaf6 in stress response, development, and virulence in B. bassiana, providing valuable insights into the molecular mechanisms governing fungal pathogenesis and potential targets for pest management strategies.
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  • 文章类型: Journal Article
    乳酸,代谢副产物,已被公认为具有高度影响力的信号分子。Lactylation,一种源自乳酸的翻译后修饰的新兴形式,在许多细胞过程中起着至关重要的作用,如炎症,胚胎发育,肿瘤增殖,和新陈代谢。然而,确切的分子机制,通过它来控制这些生物学功能,在生理和病理的情况下,仍然难以捉摸。因此,必须提供全面的乳酸化概述,以阐明其在生物过程中的重要性,并为即将进行的研究奠定基础。这篇综述旨在简洁地概述在不同生物中的乳酸化修饰过程和蛋白质乳酸化的表征。此外,总结了细胞过程和特定疾病中乳酸化的调节机制。最后,这篇综述总结了目前在乳酸化方面的研究差距,并提出了未来研究的主要方向。
    Lactate, a metabolic byproduct, has gained recognition as a highly influential signaling molecule. Lactylation, an emerging form of post-translational modification derived from lactate, plays a crucial role in numerous cellular processes such as inflammation, embryonic development, tumor proliferation, and metabolism. However, the precise molecular mechanisms through which lactylation governs these biological functions in both physiological and pathological contexts remain elusive. Hence, it is imperative to provide a comprehensive overview of lactylation in order to elucidate its significance in biological processes and establish a foundation for forthcoming investigations. This review aims to succinctly outline the process of lactylation modification and the characterization of protein lactylation across diverse organisms. Additionally, A summary of the regulatory mechanisms of lactylation in cellular processes and specific diseases is presented. Finally, this review concludes by delineating existing research gaps in lactylation and proposing primary directions for future investigations.
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  • 文章类型: Journal Article
    病毒利用宿主细胞机制来实现感染和繁殖。这篇综述讨论了DNA病毒与宿主相互作用的复杂景观,主要关注疱疹病毒和腺病毒,在受感染细胞的细胞核中复制,和牛痘病毒,在细胞质中复制。我们讨论了用于发现和验证宿主蛋白与病毒基因组相互作用的实验方法,以及这些相互作用如何影响感染过程中发生的过程。包括宿主DNA损伤反应和病毒基因组复制,修复,和转录。我们重点介绍了有关病毒-宿主蛋白相互作用的知识现状,并概述了新兴领域和未来的研究方向。
    Viruses exploit the host cell machinery to enable infection and propagation. This review discusses the complex landscape of DNA virus-host interactions, focusing primarily on herpesviruses and adenoviruses, which replicate in the nucleus of infected cells, and vaccinia virus, which replicates in the cytoplasm. We discuss experimental approaches used to discover and validate interactions of host proteins with viral genomes and how these interactions impact processes that occur during infection, including the host DNA damage response and viral genome replication, repair, and transcription. We highlight the current state of knowledge regarding virus-host protein interactions and also outline emerging areas and future directions for research.
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  • 文章类型: Journal Article
    单链DNA(ssDNA)对于真核生物和原核生物中的各种DNA模板化过程至关重要。然而,与非植物系统相比,植物中ssDNA的综合表征仍然滞后。这里,我们进行了原位S1-seq(ISS1-seq),起始gDNA从5µg到250ng,其次是水稻(OryzasativaL.)中ssDNA的全面表征。我们发现ssDNA基因座与非BDNA结构和功能性基因组基因座的子集基本上相关。ssDNA位点的亚型具有明显的表观遗传特征。重要的是,ssDNA可以单独作用或部分与非BDNA结构协调,功能性基因组基因座,或表观遗传标记来主动或抑制地调节基因转录,这是基因组区域依赖性的,并与RNAPolII的独特积累有关。此外,不同类型的ssDNA对水稻基因组中TEs(尤其是常见或保守的TEs)的活性和进化具有不同的影响。我们的研究展示了一种独立于抗体的技术,用于表征植物中的非BDNA结构或功能性基因组基因座。它为进一步探索ssDNA奠定了基础并填补了关键空白,非BDNA结构,或功能性基因组基因座,从而提高我们对它们在植物中的生物学的理解。
    Single-stranded DNA (ssDNA) is essential for various DNA-templated processes in both eukaryotes and prokaryotes. However, comprehensive characterizations of ssDNA still lag in plants compared to non-plant systems. Here, we conducted in situ S1-seq (ISS1-seq), with starting gDNA ranging from 5 µg to 250 ng, followed by comprehensive characterizations of ssDNA in rice (Oryza sativa L.). We found that ssDNA loci were substantially associated with a subset of non-B DNA structures and functional genomic loci. Subtypes of ssDNA loci had distinct epigenetic features. Importantly, ssDNA may act alone or partly coordinate with non-B DNA structures, functional genomic loci, or epigenetic marks to actively or repressively modulate gene transcription, which is genomic-region-dependent and associated with the distinct accumulation of RNA Pol II. Moreover, distinct types of ssDNA had differential impacts on the activities and evolution of TEs (especially common or conserved TEs) in the rice genome. Our study showcases an antibody-independent technique for characterizing non-B DNA structures or functional genomic loci in plants. It lays the groundwork and fills a crucial gap for further exploration of ssDNA, non-B DNA structures, or functional genomic loci, thereby advancing our understanding of their biology in plants.
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  • 文章类型: Journal Article
    泛素-折叠修饰剂1(UFM1)通过一系列酶促反应与蛋白质底物共价缀合,称为UFMylation的过程。UFMylation协调一系列重要的生物学功能,包括维持内质网(ER)稳态,促进蛋白质生物发生,促进细胞分化,调节DNA损伤反应,并参与癌症相关的信号通路。UFMylation在过去几年中迅速发展成为前沿研究领域之一,然而,还有很多事情有待发现。在这次审查中,首先,简要介绍了UFM化及其与疾病相关的细胞功能。然后,我们总结了鉴定UFMylation底物的蛋白质组学方法,并探讨了UFMylation对基因转录的影响,蛋白质翻译,和维持ER稳态。接下来,我们强调了UFMylation和两个蛋白质降解途径之间的复杂调节,泛素-蛋白酶体系统和自噬-溶酶体途径,并探索其作为药物靶标的潜力。最后,我们讨论了UFM化领域的新兴观点。这篇综述可能为靶向UFMylation系统的药物发现提供有价值的见解。
    Ubiquitin-fold modifier 1 (UFM1) is covalently conjugated to protein substrates via a cascade of enzymatic reactions, a process known as UFMylation. UFMylation orchestrates an array of vital biological functions, including maintaining endoplasmic reticulum (ER) homeostasis, facilitating protein biogenesis, promoting cellular differentiation, regulating DNA damage response, and participating in cancer-associated signaling pathways. UFMylation has rapidly evolved into one of the forefront research areas within the last few years, yet much remains to be uncovered. In this review, first, UFMylation and its cellular functions associated with diseases are briefly introduced. Then, we summarize the proteomic approaches for identifying UFMylation substrates and explore the impact of UFMylation on gene transcription, protein translation, and maintenance of ER homeostasis. Next, we highlight the intricate regulation between UFMylation and two protein degradation pathways, the ubiquitin-proteasome system and the autophagy-lysosome pathway, and explore the potential of UFMylation system as a drug target. Finally, we discuss emerging perspectives in the UFMylation field. This review may provide valuable insights for drug discovery targeting the UFMylation system.
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  • 文章类型: Journal Article
    控制基因转录的细胞过程的复杂景观,染色质组织,基因组稳定性是一个令人着迷的研究领域。维持这种微妙平衡的关键角色是合众情结,具有多方面作用的分子机器。这篇综述对这些复杂的联系及其对各种人类疾病的重大影响进行了深入的探索。
    The intricate landscape of cellular processes governing gene transcription, chromatin organization, and genome stability is a fascinating field of study. A key player in maintaining this delicate equilibrium is the cohesin complex, a molecular machine with multifaceted roles. This review presents an in-depth exploration of these intricate connections and their significant impact on various human diseases.
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  • 文章类型: Journal Article
    邻苯二甲酸二异丁酯(DiBP),是邻苯二甲酸二丁酯(DBP)的广泛化学替代品。尽管已在全球地表水中检测到DBP和DiBP,迄今为止,很少有研究系统地评估了DBP及其替代水生生物的风险。本研究比较了斑马鱼胚胎中DBP和DiBP的个体和关节毒性以及甲状腺激素水平。通过实时聚合酶链反应研究了与下丘脑-垂体-甲状腺(HPT)轴相关的关键基因的转录本。96h时DBP和DiBP对斑马鱼的半数致死浓度分别为0.545mgL-1和1.149mgL-1。相同比例的DBP-DiBP(0.25-0.53mgL-1)的联合毒性作用表现出协同作用。甲状腺激素水平随着暴露于10μgL-1的DBP或50μgL-1的DiBP而增加,暴露于这两种化合物显着增加甲状腺球蛋白基因(tg)的甲状腺特异性转录,氢气脱碘酶(dio2),和转甲状腺素蛋白(ttr),指示与HPT轴相关的不良反应。分子对接结果表明,DBP(-7.10kcal/M和-7.53kcal/M)和DiBP(-6.63kcal/M和-7.42kcal/M)与甲状腺激素受体具有相同的对接能量。我们的数据设施了解DBP及其替代品(DiBP)的潜在有害影响。
    Diisobutyl phthalate (DiBP), is widely chemical replacement for Dibutyl phthalate (DBP). Although DBP and DiBP have been detected in surface water worldwide, few studies to date have systematically assessed the risks of DBP and its alternatives to aquatic organisms. The present study compared DBP and DiBP for their individual and joint toxicity as well as thyroid hormone levels in zebrafish embryo. Transcripts of key genes related to the hypothalamic-pituitary-thyroid (HPT) axis were investigated in developing zebrafish larvae by application of real time polymerase chain reaction. The median half-lethal concentrations of DBP and DiBP to zebrafish at 96 h were 0.545 mg L-1 and 1.149 mg L-1, respectively. The joint toxic effect of DBP-DiBP (0.25-0.53 mg L-1) with the same ratio showed a synergistic effect. Thyroid hormones levels increased with exposure to 10 μg L-1 of DBP or 50 μg L-1 of DiBP, and exposure to both compounds significantly increased thyroid gland-specific transcription of thyroglobulin gene (tg), hyronine deiodinase (dio2), and transthyretin (ttr), indicating an adverse effect associated with the HPT axis. Molecular docking results indicated that DBP (-7.10 kcal/M and -7.53 kcal/M) and DiBP (-6.63 kcal/M and -7.42 kcal/M) had the same docking energy with thyroid hormone receptors. Our data facilities an understand of potential harmful effects of DBP and its alternative (DiBP).
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  • 文章类型: Journal Article
    背景:细菌RNA聚合酶全酶需要sigma70因子来通过鉴定启动子元件启动转录。蓝藻具有多个sigma70因子以适应各种各样的生态位。这些因子分为两类:初级sigma因子在正常生长条件下启动管家基因的转录,而替代sigma因子在特定条件下启动特定基因的转录。然而,目前的分类没有考虑其结构域的模块化组织,因此引入了多种功能和结构偏见。需要对蓝细菌中的这种蛋白质家族进行全面分析以解决这些限制。
    结果:我们研究了蓝藻中sigma70因子的结构和演化,分析它们的模块化架构和单细胞之间的变化,丝状的,和异形形成形态型。发现了4,193个sigma70同源物,具有59种不同的模块化模式,包括六个基本域名和29个附属域名,例如DUF6596。90%的蓝细菌通常具有5至17个sigma70同源物,这个数字可能取决于菌株形态类型,分类顺序和基因组大小。我们将sigma70因子分为12个氏族和36个家庭。根据分类顺序和表型性状,14个主要家庭中的同源物数量是可变的,A.1家族包括主要的sigma因子,因为该家族在所有蓝细菌物种中都被发现。发现A.1,A.5,C.1,E.1,J.1和K.1家族是区分异形形成菌株的关键sigma家族。为了解释sigma70的多样化和进化,我们提出了一种源于A1家族共同祖先多样化的进化情景。这种情况的特征是进化事件,包括域丢失,gains,插入,和修改。DUF6596结构域在细菌sigma70蛋白中的高出现,以及它与放线菌中观察到的最高患病率的关联,表明该域可能对sigma70功能很重要。这也意味着该结构域可能已经出现在放线菌中,并通过水平基因转移进行了转移。
    结论:我们的分析提供了对sigma70模块化领域架构的详细见解,引入了一种新颖的稳健分类。它还提出了一个进化场景,解释了它们在不同分类顺序之间的多样性。
    BACKGROUND: Bacterial RNA polymerase holoenzyme requires sigma70 factors to start transcription by identifying promoter elements. Cyanobacteria possess multiple sigma70 factors to adapt to a wide variety of ecological niches. These factors are grouped into two categories: primary sigma factor initiates transcription of housekeeping genes during normal growth conditions, while alternative sigma factors initiate transcription of specific genes under particular conditions. However, the present classification does not consider the modular organization of their structural domains, introducing therefore multiple functional and structural biases. A comprehensive analysis of this protein family in cyanobacteria is needed to address these limitations.
    RESULTS: We investigated the structure and evolution of sigma70 factors in cyanobacteria, analyzing their modular architecture and variation among unicellular, filamentous, and heterocyst-forming morphotypes. 4,193 sigma70 homologs were found with 59 distinct modular patterns, including six essential and 29 accessory domains, such as DUF6596. 90% of cyanobacteria typically have 5 to 17 sigma70 homologs and this number likely depends on the strain morphotype, the taxonomic order and the genome size. We classified sigma70 factors into 12 clans and 36 families. According to taxonomic orders and phenotypic traits, the number of homologs within the 14 main families was variable, with the A.1 family including the primary sigma factor since this family was found in all cyanobacterial species. The A.1, A.5, C.1, E.1, J.1, and K.1 families were found to be key sigma families that distinguish heterocyst-forming strains. To explain the diversification and evolution of sigma70, we propose an evolutionary scenario rooted in the diversification of a common ancestor of the A1 family. This scenario is characterized by evolutionary events including domain losses, gains, insertions, and modifications. The high occurrence of the DUF6596 domain in bacterial sigma70 proteins, and its association with the highest prevalence observed in Actinobacteria, suggests that this domain might be important for sigma70 function. It also implies that the domain could have emerged in Actinobacteria and been transferred through horizontal gene transfer.
    CONCLUSIONS: Our analysis provides detailed insights into the modular domain architecture of sigma70, introducing a novel robust classification. It also proposes an evolutionary scenario explaining their diversity across different taxonomical orders.
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