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The complex non-genetic inheritance of complex traits 复杂性状的非遗传复杂性
IF 39.1 1区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2024-08-29 DOI: 10.1038/s41576-024-00770-6
Merly C. Vogt
Merly C. Vogt recalls a seminal paper by Greer et al., who demonstrated the transgenerational inheritance of longevity, a complex trait, in Caenorhabditis elegans by manipulating the trimethylation of histone H3 lysine 4 (H3K4me3) in the parental generation.
Merly C. Vogt 回顾了 Greer 等人的一篇开创性论文,他们通过操纵亲代中组蛋白 H3 赖氨酸 4 的三甲基化(H3K4me3),证明了秀丽隐杆线虫(Caenorhabditis elegans)长寿这一复杂性状的跨代遗传。
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引用次数: 0
Convergent evolution of prickles across crops 作物皮刺的趋同进化。
IF 39.1 1区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2024-08-22 DOI: 10.1038/s41576-024-00771-5
Henry Ertl
Satterlee et al. employ several approaches to demonstrate that prickle evolution has a common genetic basis among several plant lineages.
Satterlee 等人采用多种方法证明,皮刺的进化在多个植物品系中具有共同的遗传基础。
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引用次数: 0
Mosaic variegated aneuploidy in development, ageing and cancer 发育、衰老和癌症中的镶嵌变异非整倍体
IF 39.1 1区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2024-08-21 DOI: 10.1038/s41576-024-00762-6
Marcos Malumbres, Carolina Villarroya-Beltri
Mosaic variegated aneuploidy (MVA) is a rare condition in which abnormal chromosome counts (that is, aneuploidies), affecting different chromosomes in each cell (making it variegated) are found only in a certain number of cells (making it mosaic). MVA is characterized by various developmental defects and, despite its rarity, presents a unique clinical scenario to understand the consequences of chromosomal instability and copy number variation in humans. Research from patients with MVA, genetically engineered mouse models and functional cellular studies have found the genetic causes to be mutations in components of the spindle-assembly checkpoint as well as in related proteins involved in centrosome dynamics during mitosis. MVA is accompanied by tumour susceptibility (depending on the genetic basis) as well as cellular and systemic stress, including chronic immune response and the associated clinical implications. Mosaic variegated aneuploidy is a rare condition in which the copy number of different chromosomes varies across some cells within an individual. In this Review, the authors discuss the genetic underpinnings and clinical manifestations of this condition and relate these findings to the consequences of chromosomal instability more broadly.
马赛克变异非整倍体(MVA)是一种罕见病,即染色体数目异常(即非整倍体),影响每个细胞中的不同染色体(使其成为变异体),但只在一定数量的细胞中发现(使其成为马赛克体)。MVA以各种发育缺陷为特征,尽管罕见,却为了解人类染色体不稳定性和拷贝数变异的后果提供了一个独特的临床场景。通过对子宫内膜异位症患者、基因工程小鼠模型和功能性细胞研究的研究发现,其遗传原因是纺锤体组装检查点以及有丝分裂过程中参与中心体动力学的相关蛋白的突变。中枢神经系统疾病伴随着肿瘤易感性(取决于遗传基础)以及细胞和全身压力,包括慢性免疫反应和相关的临床影响。
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引用次数: 0
Multifunctional histone variants in genome function 基因组功能中的多功能组蛋白变体
IF 42.7 1区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2024-08-13 DOI: 10.1038/s41576-024-00759-1
Lee H. Wong, David J. Tremethick

Histones are integral components of eukaryotic chromatin that have a pivotal role in the organization and function of the genome. The dynamic regulation of chromatin involves the incorporation of histone variants, which can dramatically alter its structural and functional properties. Contrary to an earlier view that limited individual histone variants to specific genomic functions, new insights have revealed that histone variants exert multifaceted roles involving all aspects of genome function, from governing patterns of gene expression at precise genomic loci to participating in genome replication, repair and maintenance. This conceptual change has led to a new understanding of the intricate interplay between chromatin and DNA-dependent processes and how this connection translates into normal and abnormal cellular functions.

组蛋白是真核染色质不可或缺的组成部分,在基因组的组织和功能中发挥着关键作用。染色质的动态调控涉及组蛋白变体的结合,而组蛋白变体可显著改变染色质的结构和功能特性。早先的观点认为,单个组蛋白变体仅限于发挥特定的基因组功能,与此相反,新的研究发现,组蛋白变体发挥着多方面的作用,涉及基因组功能的方方面面,从管理精确基因组位点的基因表达模式,到参与基因组的复制、修复和维护。这种概念上的变化使人们对染色质和 DNA 依赖过程之间错综复杂的相互作用以及这种联系如何转化为正常和异常的细胞功能有了新的认识。
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引用次数: 0
DNA methylation in mammalian development and disease 哺乳动物发育和疾病中的 DNA 甲基化
IF 42.7 1区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2024-08-12 DOI: 10.1038/s41576-024-00760-8
Zachary D. Smith, Sara Hetzel, Alexander Meissner

The DNA methylation field has matured from a phase of discovery and genomic characterization to one seeking deeper functional understanding of how this modification contributes to development, ageing and disease. In particular, the past decade has seen many exciting mechanistic discoveries that have substantially expanded our appreciation for how this generic, evolutionarily ancient modification can be incorporated into robust epigenetic codes. Here, we summarize the current understanding of the distinct DNA methylation landscapes that emerge over the mammalian lifespan and discuss how they interact with other regulatory layers to support diverse genomic functions. We then review the rising interest in alternative patterns found during senescence and the somatic transition to cancer. Alongside advancements in single-cell and long-read sequencing technologies, the collective insights made across these fields offer new opportunities to connect the biochemical and genetic features of DNA methylation to cell physiology, developmental potential and phenotype.

DNA 甲基化领域已经从发现和基因组特征描述阶段成熟到寻求对这种修饰如何促进发育、衰老和疾病的更深入的功能性理解阶段。尤其是在过去的十年中,许多令人振奋的机理发现大大扩展了我们对这一古老的进化修饰如何被纳入强大的表观遗传密码的认识。在此,我们总结了目前对哺乳动物生命周期中出现的不同 DNA 甲基化景观的理解,并讨论了它们如何与其他调控层相互作用以支持不同的基因组功能。然后,我们回顾了人们对衰老和体细胞向癌症转化过程中发现的替代模式日益增长的兴趣。随着单细胞和长读程测序技术的进步,这些领域的共同见解为将 DNA 甲基化的生化和遗传特征与细胞生理、发育潜能和表型联系起来提供了新的机会。
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引用次数: 0
Position-dependent effects of transcription factor binding 转录因子结合的位置依赖效应
IF 39.1 1区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2024-08-12 DOI: 10.1038/s41576-024-00769-z
Kirsty Minton
Duttke et al. show that transcription factors have position-dependent effects relative to their distance from the transcription start site, which suggests that a ''spatial grammar'' could be used to encode multiple gene-regulatory programmes.
Duttke 等人的研究表明,转录因子与转录起始位点的距离会产生位置依赖性效应,这表明 "空间语法 "可用于编码多种基因调控程序。
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引用次数: 0
Reconstructing generation intervals over time 随着时间的推移重建世代间隔
IF 39.1 1区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2024-08-05 DOI: 10.1038/s41576-024-00766-2
Pablo Librado
In this Tools of the Trade article, Pablo Librado describes a novel computational method to infer the time between successive generations from genomic data, including ancient genomes, which offers new insights into the timing of evolutionary and demographic events.
在这篇 "贸易工具 "文章中,巴勃罗-利布拉多(Pablo Librado)介绍了一种新颖的计算方法,这种方法可以从基因组数据(包括古代基因组)中推断出连续世代之间的时间,从而为了解进化和人口事件的时间提供了新的视角。
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引用次数: 0
Chromosomal instability as a driver of cancer progression 染色体不稳定性是癌症进展的驱动因素
IF 42.7 1区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2024-07-29 DOI: 10.1038/s41576-024-00761-7
Xuelan Chen, Albert S. Agustinus, Jun Li, Melody DiBona, Samuel F. Bakhoum

Chromosomal instability (CIN) refers to an increased propensity of cells to acquire structural and numerical chromosomal abnormalities during cell division, which contributes to tumour genetic heterogeneity. CIN has long been recognized as a hallmark of cancer, and evidence over the past decade has strongly linked CIN to tumour evolution, metastasis, immune evasion and treatment resistance. Until recently, the mechanisms by which CIN propels cancer progression have remained elusive. Beyond the generation of genomic copy number heterogeneity, recent work has unveiled additional tumour-promoting consequences of abnormal chromosome segregation. These mechanisms include complex chromosomal rearrangements, epigenetic reprogramming and the induction of cancer cell-intrinsic inflammation, emphasizing the multifaceted role of CIN in cancer.

染色体不稳定性(CIN)是指细胞在分裂过程中获得染色体结构和数量异常的倾向性增加,从而导致肿瘤遗传异质性。CIN 长期以来一直被认为是癌症的标志,过去十年的证据表明,CIN 与肿瘤演变、转移、免疫逃避和耐药性密切相关。直到最近,CIN 推动癌症进展的机制仍然扑朔迷离。除了基因组拷贝数异质性的产生,最近的研究揭示了染色体分离异常的其他肿瘤促进后果。这些机制包括复杂的染色体重排、表观遗传学重编程和诱导癌细胞内在炎症,从而强调了 CIN 在癌症中的多方面作用。
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引用次数: 0
Epigenetic editing works like a CHARM 表观遗传编辑就像 "CHARM "一样有效
IF 39.1 1区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2024-07-22 DOI: 10.1038/s41576-024-00765-3
Kirsty Minton
Neumann, Bertozzi et al. describe a novel epigenetic editor termed CHARM and report its use to silence prion protein expression in the brain.
Neumann、Bertozzi 等人描述了一种被称为 CHARM 的新型表观遗传编辑器,并报告了使用该编辑器抑制大脑中朊病毒蛋白表达的情况。
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引用次数: 0
Evolution and regulation of animal sex chromosomes. 动物性染色体的进化与调控。
IF 39.1 1区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2024-07-18 DOI: 10.1038/s41576-024-00757-3
Zexian Zhu, Lubna Younas, Qi Zhou

Animal sex chromosomes typically carry the upstream sex-determining gene that triggers testis or ovary development and, in some species, are regulated by global dosage compensation in response to functional decay of the Y chromosome. Despite the importance of these pathways, they exhibit striking differences across species, raising fundamental questions regarding the mechanisms underlying their evolutionary turnover. Recent studies of non-model organisms, including insects, reptiles and teleosts, have yielded a broad view of the diversity of sex chromosomes that challenges established theories. Moreover, continued studies in model organisms with recently developed technologies have characterized the dynamics of sex determination and dosage compensation in three-dimensional nuclear space and at single-cell resolution. Here, we synthesize recent insights into sex chromosomes from a variety of species to review their evolutionary dynamics with respect to the canonical model, as well as their diverse mechanisms of regulation.

动物的性染色体通常携带触发睾丸或卵巢发育的上游性别决定基因,在某些物种中,性染色体还受到全局剂量补偿的调控,以应对Y染色体的功能衰减。尽管这些途径非常重要,但它们在不同物种间却表现出惊人的差异,这就提出了有关其进化更替机制的基本问题。最近对包括昆虫、爬行动物和长臂猿在内的非模式生物的研究,为性染色体的多样性提供了一个广阔的视角,对既有理论提出了挑战。此外,利用新近开发的技术对模式生物进行的持续研究已在三维核空间和单细胞分辨率上描述了性别决定和剂量补偿的动态特征。在此,我们综合了最近对不同物种性染色体的研究结果,回顾了它们相对于经典模型的进化动态,以及它们多种多样的调控机制。
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引用次数: 0
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Nature Reviews Genetics
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