transregulation

反式调节
  • 文章类型: Journal Article
    寻找控制蜱和蜱传播疾病的目标一直是一个持续存在的问题,到目前为止,我们仍然需要高效,用于此目的的非化学替代品。此搜索必须考虑新的替代方案。例如,基因组学分析是兽医健康研究中用于控制病原体的广泛应用工具。另一方面,我们认为,内分泌机制的调节是生物防治蜱感染的可行替代方案。因此,我们通过RT-PCR在蜱卵巢中进行了一种称为RmERR的微小触毛雌激素相关受体基因的分子鉴定,胚胎细胞,和血淋巴,这使我们能够分析其表达并提出内分泌机制和发育阶段的潜在功能。此外,我们进行了计算机表征,以探索RmERR与不同雌激素的分子相互作用,雌激素拮抗剂,和内分泌干扰物双酚A(BPA),发现通过对接分析预测并由ΔG的负值支持的潜在相互作用(这表明RmERR与评估的分子的潜在相互作用)。此外,系统发育重建表明,RmERR与其他蜱物种归为一组,但在系统发育上与宿主脊椎动物ERR相距遥远。总之,这项研究首次鉴定了牛tickR.microplus中的ERR,并提出了其与不同雌激素的相互作用,支持蜱类中可能的越位调节过程的想法。对这种相互作用及其机制的阐明揭示了其作为开发滴答控制策略的目标的潜力。
    The search for targets to control ticks and tick-borne diseases has been an ongoing problem, and so far, we still need efficient, non-chemical alternatives for this purpose. This search must consider new alternatives. For example genomics analysis is a widely applied tool in veterinary health studies to control pathogens. On the other hand, we propose that regulation of endocrine mechanisms represents a feasible alternative to biologically controlling tick infestations. Thus, we performed the molecular identification of an estrogen-related receptor gene of Rhipicephalus microplus called RmERR by RT-PCR in tick ovaries, embryonic cells, and hemolymph, which allowed us to analyze its expression and propose potential functions in endocrine mechanisms and developmental stages. In addition, we performed an in silico characterization to explore the molecular interactions of RmERR with different estrogens, estrogenic antagonists, and endocrine disruptor Bisphenol A (BPA), finding potential interactions predicted by docking analysis and supported by negative values of ΔG (which suggests the potential interaction of RmERR with the molecules evaluated). Additionally, phylogenetic reconstruction revealed that RmERR is grouped with other tick species but is phylogenetically distant from host vertebrates\' ERRs. In summary, this study allowed for the identification of an ERR in cattle tick R. microplus for the first time and suggested its interaction with different estrogens, supporting the idea of a probable transregulation process in ticks. The elucidation of this interaction and its mechanisms unveiled its potential as a target to develop tick control strategies.
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  • 文章类型: Journal Article
    糖皮质激素(GC)是参与昼夜节律适应和应激反应的激素,并且还值得注意的是,这些甾体分子通过GC受体(GR)表现出有效的抗炎作用。在配体介导的激活后,GR易位到细胞核,调节与代谢相关的基因表达,急性期反应和先天免疫反应。GR的研究领域在过去的几十年里有了很大的发展,提供多种机制,有助于理解转录调控,也影响治疗炎性疾病的药物设计。细胞过程中的液-液相分离(LLPS)代表了生物学中的一个最新主题,该主题将无膜细胞器和微环境概念化,或抑制,蛋白质或核酸的化学反应和相互作用。这些分子缩合物的形成与基因表达控制有关,和最近的证据表明,GR和其他类固醇受体可以成核相分离(PS)。在这里,我们简要回顾了GR转录控制的各种机制,这些研究主要是在炎症的背景下进行的,并进一步介绍了PS如何参与基因表达的控制。最后,我们考虑在转录控制过程中LLPS的报道进展,特别是类固醇激素受体,可能会影响不同的GR作用方式对基因表达的影响,在糖皮质激素信号转导中增加了一个新的可信分子事件。
    Glucocorticoids (GCs) are hormones involved in circadian adaptation and stress response, and it is also noteworthy that these steroidal molecules present potent anti-inflammatory action through GC receptors (GR). Upon ligand-mediated activation, GR translocates to the nucleus, and regulates gene expression related to metabolism, acute-phase response and innate immune response. GR field of research has evolved considerably in the last decades, providing varied mechanisms that contributed to the understanding of transcriptional regulation and also impacted drug design for treating inflammatory diseases. Liquid-liquid phase separation (LLPS) in cellular processes represents a recent topic in biology that conceptualizes membraneless organelles and microenvironments that promote, or inhibit, chemical reactions and interactions of protein or nucleic acids. The formation of these molecular condensates has been implicated in gene expression control, and recent evidence shows that GR and other steroid receptors can nucleate phase separation (PS). Here we briefly review the varied mechanisms of transcriptional control by GR, which are largely studied in the context of inflammation, and further present how PS can be involved in the control of gene expression. Lastly, we consider how the reported advances on LLPS during transcription control, specially for steroid hormone receptors, could impact the different modalities of GR action on gene expression, adding a new plausible molecular event in glucocorticoid signal transduction.
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  • 文章类型: Journal Article
    染色体外环状DNA(eccDNA)是一类特殊的来源于线性染色体的DNA。它与细胞核中的线性染色体独立共存。eccDNA已在多种生物体中被鉴定,包括智人,并已被证明与肿瘤进展和耐药性有关的重要作用。迄今为止,为eccDNA检测开发的计算工具仅适用于块状组织。使用计算方法在单细胞水平研究eccDNA将阐明细胞背景下eccDNA的异质性和细胞类型特异性景观。这里,我们使用成人和儿童胶质母细胞瘤(GBM)样本中转座酶可接近染色质的单细胞测序分析(scATAC-seq)产生的数据,在单细胞水平进行了首次eccDNA分析.多形性胶质母细胞瘤(GBM)是中枢神经系统的侵袭性肿瘤,预后不良。我们的分析提供了细胞起源的概述,基因组分布,以及在GBM开放染色质区域的疾病和细胞类型特定条件下线性和环状基因组之间的差异调节。我们专注于一些eccDNA元件,这些元件是以反式调节方式起作用的潜在移动增强子。总之,这项初步研究揭示了脑肿瘤细胞环境中的新eccDNA特征,支持在单细胞水平上进行eccDNA调查的强烈需求。
    Extrachromosomal circular DNA (eccDNA) is a special class of DNA derived from linear chromosomes. It coexists independently with linear chromosomes in the nucleus. eccDNA has been identified in multiple organisms, including Homo sapiens, and has been shown to play important roles relevant to tumor progression and drug resistance. To date, computational tools developed for eccDNA detection are only applicable to bulk tissue. Investigating eccDNA at the single-cell level using a computational approach will elucidate the heterogeneous and cell-type-specific landscape of eccDNA within cellular context. Here, we performed the first eccDNA analysis at the single-cell level using data generated by single-cell Assay for Transposase-Accessible Chromatin with sequencing (scATAC-seq) in adult and pediatric glioblastoma (GBM) samples. Glioblastoma multiforme (GBM) is an aggressive tumor of the central nervous system with a poor prognosis. Our analysis provides an overview of cellular origins, genomic distribution, as well as the differential regulations between linear and circular genome under disease- and cell-type-specific conditions across the open chromatin regions in GBM. We focused on some eccDNA elements that are potential mobile enhancers acting in a trans-regulation manner. In summary, this pilot study revealed novel eccDNA features in the cellular context of brain tumor, supporting the strong need for eccDNA investigation at the single-cell level.
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  • 文章类型: Journal Article
    The in vitro effect of progesterone in T. canis larvae on their enlargement and motility were evaluated, together to the possible presence of progesterone receptors (PRs). T. canis larvae were cultured in RPMI-1640 with different concentrations of progesterone (0, 20, 40, 80, 400 and 800 ng/mL). Enlargement and increases in motility were dependent on the concentration only from 0 to 80 ng/mL (p < 0.05). The mean percentage of PR + cells in newly obtained larvae as measured by flow cytometry was 8.16 ± 0.4. The number of PR + cells increased depending on concentration from 0 to 80 ng/mL (p < 0.001). Cells obtained from larvae stimulated at any of the studied hormone concentrations showed greater mean fluorescence intensity when compared to non-stimulated cells. Additionally, the expression and location of PR + cells were determined in the larvae. The sequence of an amplicon (420-bp) obtained by PCR from T. canis larvae showed 100% homology with a gene fragment that codes for the PR of the dog. PR + cells were immunolocated using confocal microscopy in the intestinal region of the larvae that had been recently obtained. The results of this study show that T. canis larvae can recognize and respond to the presence of progesterone through a molecule possibly able to bind it. Since we previously observed a similar response to prolactin, we suggest that both hormones could participate sequentially in the reactivation of T. canis larvae in pregnant bitches.
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  • 文章类型: Journal Article
    F1 hybrids in Arabidopsis and crop species are uniform and high yielding. The F2 generation loses much of the yield advantage and the plants have heterogeneous phenotypes. We generated pure breeding hybrid mimic lines by recurrent selection and also selected a pure breeding small phenotype line. The hybrid mimics are almost completely homozygous with chromosome segments from each parent. Four particular chromosomal segments from C24 and 8 from Ler were present in all of the hybrid mimic lines, whereas in the F6 small phenotype line, the 12 segments were each derived from the alternative parent. Loci critical for promoting hybrid vigor may be contained in each of these 12 conserved segments. We have identified genes with similar altered expression in hybrid mimics and F1 plants but not in the small phenotype line. These genes may be critical for the generation of hybrid vigor. Analysis of transcriptomes indicated that increased expression of the transcription factor PHYTOCHROME-INTERACTING FACTOR (PIF4) may contribute to hybrid vigor by targeting the auxin biosynthesis gene YUCCA8 and the auxin signaling gene IAA29 A number of auxin responsive genes promoting leaf growth were up-regulated in the F1 hybrids and hybrid mimics, suggesting that increased auxin biosynthesis and signaling contribute to the hybrid phenotype. The hybrid mimic seeds had earlier germination as did the seeds of the F1 hybrids, indicating cosegregation of the genes for rosette size and the germination trait. Early germination may be an indicator of vigorous hybrids.
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  • 文章类型: Journal Article
    The in vitro effect of prolactin (PRL) on the growth and motility of Toxocara canis larvae was assessed. Additionally, the expression and location of prolactin receptors (PRL-Rs) were determined in the larvae. Larvae of T. canis were incubated with different concentrations of PRL for different periods of time. The stimulated larvae accelerated their enlargement and increased their motility. The mean percentage of PRL-R+ cells in non-stimulated larvae, measured by flow cytometry was 7.3±0.3%. Compared with non-stimulated larvae, the mean fluorescence intensity (p<0.05) increased in larvae incubated with 40ng/mL of PRL for 10 days. A 465-bp length fragment was amplified from larvae gDNA by PCR. The sequence of this fragment showed 99% similarity with the gene fragment that codes for the PRL-R of the domestic dog. A high concentration of PRL-Rs was immune-located in the posterior region of the larval intestine; therefore, the intestinal cells in this region were most likely the targets for this hormone. Based on these results, PRL-Rs were identified in T. canis larvae, and the in vitro stimulation with PRL increased the number of these receptors, accelerated the growth and modified the activity of larvae. All of the above suggest that T. canis larvae are evolutionarily adapted to recognize the PRL of their definitive host and furthermore might explain the reactivation of tissue-arrested larvae during the gestation of bitches, which does not occur in gestating females of other species.
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  • 文章类型: Journal Article
    F1 hybrids can outperform their parents in yield and vegetative biomass, features of hybrid vigor that form the basis of the hybrid seed industry. The yield advantage of the F1 is lost in the F2 and subsequent generations. In Arabidopsis, from F2 plants that have a F1-like phenotype, we have by recurrent selection produced pure breeding F5/F6 lines, hybrid mimics, in which the characteristics of the F1 hybrid are stabilized. These hybrid mimic lines, like the F1 hybrid, have larger leaves than the parent plant, and the leaves have increased photosynthetic cell numbers, and in some lines, increased size of cells, suggesting an increased supply of photosynthate. A comparison of the differentially expressed genes in the F1 hybrid with those of eight hybrid mimic lines identified metabolic pathways altered in both; these pathways include down-regulation of defense response pathways and altered abiotic response pathways. F6 hybrid mimic lines are mostly homozygous at each locus in the genome and yet retain the large F1-like phenotype. Many alleles in the F6 plants, when they are homozygous, have expression levels different to the level in the parent. We consider this altered expression to be a consequence of transregulation of genes from one parent by genes from the other parent. Transregulation could also arise from epigenetic modifications in the F1. The pure breeding hybrid mimics have been valuable in probing the mechanisms of hybrid vigor and may also prove to be useful hybrid vigor equivalents in agriculture.
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