gene transcription

基因转录
  • 文章类型: Journal Article
    表观遗传调控,其特征是可逆和可遗传的遗传改变,而不改变DNA序列,最近越来越多的研究疾病。组蛋白变异调控是表观遗传调控的重要组成部分。组蛋白变体对典型组蛋白的取代深刻地改变了局部染色质结构,并调节了DNA对调节因子的可及性。从而对基因调控和DNA损伤修复产生重要影响。组蛋白H2A变体,主要包括H2A。Z,H2A.B,macroH2A,H2A。X,是具有最大序列多样性的所有组蛋白变体中最丰富的鉴定变体。具有不同的染色质占用和结构,组蛋白H2A变体在基因转录和DNA损伤修复中执行不同的功能。它们与多种病理生理机制和不同疾病的出现有关。癌症,胚胎发育异常,神经系统疾病,代谢性疾病,和心脏病都与组蛋白H2A变异有关。本文综述了H2A组蛋白变异体在哺乳动物中的功能,包括H2A。Z,H2A.B,macroH2A,H2A。X,以及他们目前在各种疾病中的作用。
    Epigenetic regulation, which is characterized by reversible and heritable genetic alterations without changing DNA sequences, has recently been increasingly studied in diseases. Histone variant regulation is an essential component of epigenetic regulation. The substitution of canonical histones by histone variants profoundly alters the local chromatin structure and modulates DNA accessibility to regulatory factors, thereby exerting a pivotal influence on gene regulation and DNA damage repair. Histone H2A variants, mainly including H2A.Z, H2A.B, macroH2A, and H2A.X, are the most abundant identified variants among all histone variants with the greatest sequence diversity. Harboring varied chromatin occupancy and structures, histone H2A variants perform distinct functions in gene transcription and DNA damage repair. They are implicated in multiple pathophysiological mechanisms and the emergence of different illnesses. Cancer, embryonic development abnormalities, neurological diseases, metabolic diseases, and heart diseases have all been linked to histone H2A variant alterations. This review focuses on the functions of H2A histone variants in mammals, including H2A.Z, H2A.B, macroH2A, and H2A.X, and their current roles in various diseases.
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  • 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
    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
    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
    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
    组蛋白伴侣和组蛋白变体在DNA复制中起关键作用,基因转录,和真核生物的DNA修复。组蛋白伴侣通过掺入或驱逐组蛋白和组蛋白变体以调节染色质可及性,可逆地促进核小体的组装和分解。从而改变染色质状态并调节DNA相关的生物过程。辅因子帮助组蛋白伴侣靶向特定染色质区域以调节组蛋白和组蛋白变体的交换。在这次审查中,我们总结了植物中组蛋白变异体与伴侣相互作用的最新进展。我们讨论了伴侣-组蛋白复合物的结构基础及其在调节基因转录和植物发育中的合作机制。
    Histone chaperones and histone variants play crucial roles in DNA replication, gene transcription, and DNA repair in eukaryotes. Histone chaperones reversibly promote nucleosome assembly and disassembly by incorporating or evicting histones and histone variants to modulate chromatin accessibility, thereby altering the chromatin states and modulating DNA-related biological processes. Cofactors assist histone chaperones to target specific chromatin regions to regulate the exchange of histones and histone variants. In this review, we summarize recent progress in the interplay between histone variants and chaperones in plants. We discuss the structural basis of chaperone-histone complexes and the mechanisms of their cooperation in regulating gene transcription and plant development.
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  • 文章类型: Journal Article
    农田土壤生物经常遇到其生存环境中存在的农药混合物。然而,土壤动物用来应对这种复合污染的潜在毒性机制尚待探索。这项研究旨在揭示毒死蜱(CPF)和氯氟氰菊酯(LCT)共同暴露在蚯蚓(Eiseniafetida)中细胞和mRNA水平的变化。结果表明,CPF和LCT的组合对动物产生了急性协同影响。大多数暴露导致总超氧化物歧化酶(T-SOD)活性的显着变化,铜/锌超氧化物歧化酶(Cu/Zn-SOD),与基础水平相比,caspase3和羧酸酯酶(CarE)。此外,当暴露于化学混合物时,四个基因的转录水平[热休克蛋白70(hsp70),gst,草皮,和calreticulin(crt)]与他们的个体暴露相比也显示出更明显的变化。确定参数的这些变化表明氧化应激的发生,细胞死亡,排毒功能障碍,同时暴露于CPF和LCT后的内质网损伤。在不同终点对CPF和LCT的混合物毒性进行全面检查将有助于了解它们对土壤无脊椎动物的总体毒性。这些农药在混合物中的有害作用增加,这表明混合物的毒性评估对于农药混合物的安全性评估和应用是必要的。
    Farmland soil organisms frequently encounter pesticide mixtures presented in their living environment. However, the underlying toxic mechanisms employed by soil animals to cope with such combined pollution have yet to be explored. This investigation aimed to reveal the changes in cellular and mRNA levels under chlorpyrifos (CPF) and lambda-cyhalothrin (LCT) co-exposures in earthworms (Eisenia fetida). Results exhibited that the combination of CPF and LCT triggered an acute synergistic influence on the animals. Most exposures resulted in significant alterations in the activities of total superoxide dismutase (T-SOD), copper/zinc superoxide dismutase (Cu/Zn-SOD), caspase 3, and carboxylesterase (CarE) compared to the basal level. Moreover, when exposed to chemical mixtures, the transcription levels of four genes [heat shock protein 70 (hsp70), gst, sod, and calreticulin (crt)] also displayed more pronounced changes compared with their individual exposures. These changes in determined parameters indicated the occurrence of oxidative stress, cell death, detoxification dysfunction, and endoplasmic reticulum damage after co-exposure to CPF and LCT in E. fetida. The comprehensive examination of mixture toxicities of CPF and LCT at different endpoints would help to understand the overall toxicity they cause to soil invertebrates. The augmented deleterious effect of these pesticides in a mixture suggested that mixture toxicity assessment was necessary for the safety evaluation and application of pesticide mixtures.
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  • 文章类型: Journal Article
    II类组蛋白脱乙酰酶(HDAC)在T细胞发育过程中对基因转录的调节很重要。然而,我们对其细胞特异性功能的理解是有限的。在这项研究中,我们发现IIa类Hdac4和Hdac7(Hdac4/7)在转录中被选择性诱导,指导小鼠T辅助细胞17(Th17)细胞从幼稚CD4T细胞的谱系特异性分化。重要的是,Hdac4/7在其他Th亚型中在功能上是可有可无的。机械上,Hdac4与转录因子(TF)JunB相互作用,促进Th17标记基因如Il17a/f的转录激活。相反,Hdac7与TFAiolos和Smrt/Ncor1-Hdac3协同抑制因子来抑制Th17负调节因子的转录,包括Il2,在Th17细胞分化。通过药理学或遗传学方法抑制Hdac4/7有效减轻结肠炎小鼠模型中Th17细胞介导的肠道炎症。我们的研究揭示了HDAC4和HDAC7在Th17细胞分化过程中在调控有序基因转录方面具有独特但协同作用的分子机制。这些发现提示了靶向HDAC4/7治疗Th17相关炎性疾病的潜在治疗策略。如溃疡性结肠炎。
    Class II histone deacetylases (HDACs) are important in regulation of gene transcription during T cell development. However, our understanding of their cell-specific functions is limited. In this study, we reveal that class IIa Hdac4 and Hdac7 (Hdac4/7) are selectively induced in transcription, guiding the lineage-specific differentiation of mouse T-helper 17 (Th17) cells from naive CD4+ T cells. Importantly, Hdac4/7 are functionally dispensable in other Th subtypes. Mechanistically, Hdac4 interacts with the transcription factor (TF) JunB, facilitating the transcriptional activation of Th17 signature genes such as Il17a/f. Conversely, Hdac7 collaborates with the TF Aiolos and Smrt/Ncor1-Hdac3 corepressors to repress transcription of Th17 negative regulators, including Il2, in Th17 cell differentiation. Inhibiting Hdac4/7 through pharmacological or genetic methods effectively mitigates Th17 cell-mediated intestinal inflammation in a colitis mouse model. Our study uncovers molecular mechanisms where HDAC4 and HDAC7 function distinctively yet cooperatively in regulating ordered gene transcription during Th17 cell differentiation. These findings suggest a potential therapeutic strategy of targeting HDAC4/7 for treating Th17-related inflammatory diseases, such as ulcerative colitis.
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