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Exploring new roles for RNA-binding proteins in epigenetic and gene regulation 探索 RNA 结合蛋白在表观遗传和基因调控中的新作用。
IF 4 2区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-12-20 DOI: 10.1016/j.gde.2023.102136
Pedro Avila-Lopez , Shannon M Lauberth

A significant portion of the human proteome comprises RNA-binding proteins (RBPs) that play fundamental roles in numerous biological processes. In the last decade, there has been a staggering increase in RBP identification and classification, which has fueled interest in the evolving roles of RBPs and RBP-driven molecular mechanisms. Here, we focus on recent insights into RBP-dependent regulation of the epigenetic and transcriptional landscape. We describe advances in methodologies that define the RNA-protein interactome and machine-learning algorithms that are streamlining RBP discovery and predicting new RNA-binding regions. Finally, we present how RBP dysregulation leads to alterations in tumor-promoting gene expression and discuss the potential for targeting these RBPs for the development of new cancer therapeutics.

人类蛋白质组中有很大一部分是 RNA 结合蛋白(RBPs),它们在许多生物过程中发挥着重要作用。在过去的十年中,RBP 的鉴定和分类有了惊人的增长,这激发了人们对 RBP 不断演变的作用和 RBP 驱动的分子机制的兴趣。在此,我们重点介绍最近对 RBP 依赖性调控表观遗传和转录格局的深入研究。我们介绍了定义 RNA 蛋白相互作用组的方法学进展,以及简化 RBP 发现和预测新 RNA 结合区的机器学习算法。最后,我们介绍了 RBP 失调如何导致肿瘤促进基因表达的改变,并讨论了靶向这些 RBPs 开发癌症新疗法的潜力。
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引用次数: 0
Polycomb repressive complex 2 accessory factors: rheostats for cell fate decision? 多聚胞抑制复合体 2 辅助因子:细胞命运决定的调节器?
IF 4 2区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-12-12 DOI: 10.1016/j.gde.2023.102137
Hina Bharti , Sungwook Han , Han-Wen Chang , Danny Reinberg

Epigenetic reprogramming during development is key to cell identity and the activities of the Polycomb repressive complexes are vital for this process. We focus on polycomb repressive complex 2 (PRC2), which catalyzes H3K27me1/2/3 and safeguards cellular integrity by ensuring proper gene repression. Notably, various accessory factors associate with PRC2, strongly influencing cell fate decisions, and their deregulation contributes to various illnesses. Yet, the exact role of these factors during development and carcinogenesis is not fully understood. Here, we present recent progress toward addressing these points and an analysis of the expression levels of PRC2 accessory factors in various tissues and developmental stages to highlight their abundance and roles. Last, we evaluate their contribution to cancer-specific phenotypes, providing insight into novel anticancer therapies.

发育过程中的表观遗传重编程是细胞特性的关键,而多聚核抑制复合体的活动对这一过程至关重要。我们重点研究多聚核抑制复合体2(PRC2),它催化H3K27me1/2/3,通过确保适当的基因抑制来保障细胞的完整性。值得注意的是,各种附属因子与 PRC2 相关联,对细胞命运的决定有很大影响,它们的失调会导致各种疾病。然而,这些因子在发育和癌变过程中的确切作用还不完全清楚。在此,我们介绍了解决这些问题的最新进展,并分析了 PRC2 辅助因子在不同组织和发育阶段的表达水平,以突出它们的丰度和作用。最后,我们评估了它们对癌症特异性表型的贡献,从而为新型抗癌疗法提供启示。
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引用次数: 0
Topical section: embryonic models (2023) for Current Opinion in Genetics & Development 遗传学与发育当前观点》的专题部分:胚胎模型(2023)。
IF 4 2区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-12-05 DOI: 10.1016/j.gde.2023.102134
Charlotte E Handford , Sergi Junyent , Victoria Jorgensen , Magdalena Zernicka-Goetz

Stem cell-based mammalian embryo models facilitate the discovery of developmental mechanisms because they are more amenable to genetic and epigenetic perturbations than natural embryos. Here, we highlight exciting recent advances that have yielded a plethora of models of embryonic development. Imperfections in these models highlight gaps in our current understanding and outline future research directions, ushering in an exciting new era for embryology.

与自然胚胎相比,基于干细胞的哺乳动物胚胎模型更容易受到遗传和表观遗传扰动的影响,因此有助于发现发育机制。在此,我们重点介绍最近取得的令人兴奋的进展,这些进展产生了大量胚胎发育模型。这些模型的缺陷凸显了我们目前认识的不足,并勾勒出未来的研究方向,为胚胎学开创了一个激动人心的新时代。
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引用次数: 0
Human blastoid as an in vitro model of human blastocysts 作为人类囊胚体外模型的人类囊胚。
IF 4 2区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-12-04 DOI: 10.1016/j.gde.2023.102135
Xiaodong Liu , Jose M Polo

Human development is a highly coordinated process, with any abnormalities during the early embryonic stages that can often have detrimental consequences. The complexity and nuances of human development underpin its significance in embryo research. However, this research is often hindered by limited availability and ethical considerations associated with the use of donated blastocysts from in vitro fertilization (IVF) surplus. Human blastoids offer promising alternatives as they can be easily generated and manipulated in the laboratory while preserving key characteristics of human blastocysts. In this way, they hold the potential to serve as a scalable and ethically permissible resource in embryology research. By utilizing such human embryo models, we can establish a transformative platform that complements the study with IVF embryos, ultimately enhancing our understanding of human embryogenesis.

人类发育是一个高度协调的过程,胚胎早期阶段的任何异常都可能造成有害后果。人类发育的复杂性和细微差别决定了胚胎研究的重要性。然而,由于使用体外受精(IVF)剩余捐赠囊胚的可用性有限且存在伦理方面的考虑,这项研究往往受到阻碍。人类囊胚提供了很有前景的替代品,因为它们可以很容易地在实验室中生成和操作,同时保留人类囊胚的主要特征。因此,它们有可能成为胚胎学研究中可扩展且符合伦理要求的资源。通过利用这种人类胚胎模型,我们可以建立一个变革性平台,对体外受精胚胎研究进行补充,最终提高我们对人类胚胎发生的认识。
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引用次数: 0
New perspectives on the causes and consequences of male meiotic drive 男性减数分裂驱动的原因和后果的新观点
IF 4 2区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-12-01 DOI: 10.1016/j.gde.2023.102111
Cécile Courret , Xiaolu Wei , Amanda M Larracuente

Gametogenesis is vulnerable to selfish genetic elements that bias their transmission to the next generation by cheating meiosis. These so-called meiotic drivers are widespread in plants, animals, and fungi and can impact genome evolution. Here, we summarize recent progress on the causes and consequences of meiotic drive in males, where selfish elements attack vulnerabilities in spermatogenesis. Advances in genomics provide new insights into the organization and dynamics of driving chromosomes in natural populations. Common themes, including small RNAs, gene duplications, and heterochromatin, emerged from these studies. Interdisciplinary approaches combining evolutionary genomics with molecular and cell biology are beginning to unravel the mysteries of drive and suppression mechanisms. These approaches also provide insights into fundamental processes in spermatogenesis and chromatin regulation.

配子发生很容易受到自私的遗传因素的影响,这些遗传因素通过欺骗减数分裂将配子遗传给下一代。这些所谓的减数分裂驱动因素广泛存在于植物、动物和真菌中,并能影响基因组进化。在这里,我们总结了最近在男性减数分裂驱动的原因和后果方面的进展,其中自私元素攻击精子发生中的脆弱性。基因组学的进步为自然种群中驱动染色体的组织和动力学提供了新的见解。共同的主题,包括小rna,基因复制和异染色质,从这些研究中出现。将进化基因组学与分子和细胞生物学相结合的跨学科方法开始揭开驱动和抑制机制的奥秘。这些方法也为精子发生和染色质调节的基本过程提供了见解。
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引用次数: 0
‘Enhancing’ skeletal muscle and stem cells in three-dimensional: genome regulation of skeletal muscle in development and disease “增强”三维骨骼肌和干细胞:骨骼肌发育和疾病的基因组调控。
IF 4 2区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-11-09 DOI: 10.1016/j.gde.2023.102133
Matthew A. Romero , April D. Pyle

The noncoding genome imparts important regulatory control over gene expression. In particular, gene enhancers represent a critical layer of control that integrates developmental and differentiation signals outside the cell into transcriptional outputs inside the cell. Recently, there has been an explosion in genomic techniques to probe enhancer control, function, and regulation. How enhancers are regulated and integrate signals in stem cell development and differentiation is largely an open question. In this review, we focus on the role gene enhancers play in muscle stem cell specification, differentiation, and progression. We pay specific attention toward the identification of muscle-specific enhancers, the binding of transcription factors to these enhancers, and how enhancers communicate to their target genes via three-dimensional looping.

非编码基因组对基因表达具有重要的调控作用。特别是,基因增强子代表了一个关键的控制层,将细胞外的发育和分化信号整合到细胞内的转录输出中。最近,基因组技术在探索增强子的控制、功能和调控方面有了爆炸式的发展。在干细胞发育和分化过程中,增强子是如何调控和整合信号的,这在很大程度上是一个悬而未决的问题。在这篇综述中,我们主要关注基因增强子在肌肉干细胞的分化、分化和发展中所起的作用。我们特别关注肌肉特异性增强子的鉴定,转录因子与这些增强子的结合,以及增强子如何通过三维环与靶基因交流。
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引用次数: 0
Somatic mutation burden in relation to aging and functional life span: implications for cellular reprogramming and rejuvenation 与衰老和功能寿命相关的体细胞突变负担:对细胞重编程和再生的影响。
IF 4 2区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-11-04 DOI: 10.1016/j.gde.2023.102132
Alexander Y Maslov , Jan Vijg

The accrual of somatic mutations has been implicated as causal factors in aging since the 1950s. However, the quantitative analysis of somatic mutations has posed a major challenge due to the random nature of de novo mutations in normal tissues, which has limited analysis to tumors and other clonal lineages. Advances in single-cell and single-molecule next-generation sequencing now allow to obtain, for the first time, detailed insights into the landscape of somatic mutations in different human tissues and cell types as a function of age under various conditions. Here, we will briefly recapitulate progress in somatic mutation analysis and discuss the possible relationship between somatic mutation burden with functional life span, with a focus on differences between germ cells, stem cells, and differentiated cells.

自20世纪50年代以来,体细胞突变的增加一直被认为是衰老的原因。然而,由于正常组织中新发突变的随机性,对肿瘤和其他克隆谱系的分析有限,因此体细胞突变的定量分析带来了重大挑战。单细胞和单分子下一代测序的进展现在首次使我们能够详细了解不同条件下不同人类组织和细胞类型的体细胞突变与年龄的关系。在这里,我们将简要回顾体细胞突变分析的进展,并讨论体细胞突变负担与功能寿命之间的可能关系,重点关注生殖细胞、干细胞和分化细胞之间的差异。
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引用次数: 0
Modifying gastruloids to dissect mechanisms of tissue-specific induction 修改原肠胚以剖析组织特异性诱导的机制。
IF 4 2区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-26 DOI: 10.1016/j.gde.2023.102130
David A Turner , Jennifer Nichols

How functional organisms arise from a single cell is a fundamental question in biology with direct relevance to understanding developmental defects and diseases. Dissecting developmental processes provides the basic, critical framework for understanding disease progression and treatment. Bottom-up approaches to recapitulate formation of various components of the embryo have been effective to probe symmetry-breaking, self-organisation, tissue patterning and morphogenesis. However, these studies have been mostly concerned with axial patterning, which is essentially longitudinal. Can these models generate the appendicular axes? If so, how far can self-organisation take these? Will experimentally induced organisers be required? This short review explores these questions, highlighting how minimal models are essential for understanding patterning and morphogenetic processes.

功能性生物体如何从单个细胞中产生是生物学中的一个基本问题,与理解发育缺陷和疾病直接相关。解剖发育过程为理解疾病进展和治疗提供了基本、关键的框架。自下而上的方法来概括胚胎各个组成部分的形成,对于探索对称性破坏、自组织、组织模式和形态发生是有效的。然而,这些研究主要关注轴向图案,它本质上是纵向的。这些模型能生成阑尾轴吗?如果是这样,自我组织能走多远?是否需要实验诱导组织者?这篇简短的综述探讨了这些问题,强调了最小模型对于理解模式形成和形态发生过程至关重要。
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引用次数: 0
Editorial overview: Conflicts, conflicts everywhere 编辑综述:冲突无处不在。
IF 4 2区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-20 DOI: 10.1016/j.gde.2023.102131
Harmit S Malik, Judith E Mank
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引用次数: 0
Divergent outcomes of genetic conflict on the UV sex chromosomes of Marchantia polymorpha and Ceratodon purpureus 紫外性染色体遗传冲突的不同结果。
IF 4 2区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-20 DOI: 10.1016/j.gde.2023.102129
Stuart F McDaniel

In species with separate sexes, the genome must produce two distinct developmental programs. Sexually dimorphic development may be controlled by either sex-limited loci or biased expression of loci transmitted through both sexes. Variation in the gene content of sex-limited chromosomes demonstrates that eukaryotic species differ markedly in the roles of these two mechanisms in governing sexual dimorphism. The bryophyte model systems Marchantia polymorpha and Ceratodon purpureus provide a particularly striking contrast. Although both species possess a haploid UV sex chromosome system, in which females carry a U chromosome and males carry a V, M. polymorpha relies on biased autosomal expression, while in C. purpureus, sex-linked genes drive dimorphism. Framing these genetic architectures as divergent outcomes of genetic conflict highlights comparative genomic analyses to better understand the evolution of sexual dimorphism.

在性别不同的物种中,基因组必须产生两个不同的发育程序。性别二型发育可能受到性别限制基因座或通过两性传播的基因座的偏向性表达的控制。性别受限染色体基因含量的变化表明,真核生物物种在控制两性异形方面,这两种机制的作用明显不同。苔藓植物模型系统Marchantia polymorpha和Ceratodon purpureus形成了特别鲜明的对比。尽管这两个物种都拥有单倍体的紫外线性染色体系统,其中雌性携带U染色体,雄性携带V染色体,但多晶型M.polymorphia依赖于有偏的常染色体表达,而在紫锥虫中,性连锁基因驱动二型性。将这些遗传结构视为遗传冲突的不同结果,突出了比较基因组分析,以更好地理解两性异形的进化。
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引用次数: 0
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Current Opinion in Genetics & Development
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