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Dysregulation of transcriptional condensates in human disease: mechanisms, biological functions, and open questions 人类疾病中转录凝聚物的失调：机制、生物功能和未决问题
IF 4 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-05-23 DOI: 10.1016/j.gde.2024.102203
Kaeli M Mathias , Yiman Liu , Liling Wan
{"title":"Dysregulation of transcriptional condensates in human disease: mechanisms, biological functions, and open questions","authors":"Kaeli M Mathias ,&nbsp;Yiman Liu ,&nbsp;Liling Wan","doi":"10.1016/j.gde.2024.102203","DOIUrl":"https://doi.org/10.1016/j.gde.2024.102203","url":null,"abstract":"<div><p>Precise gene expression, crucial for normal development and health, depends on the co-ordinated assembly and function of various factors within the crowded nucleus. Recent evidence suggests that this process is in part regulated by mesoscale compartmentalization and concentration of transcriptional components within condensates, offering a new perspective on gene regulation. Dysregulation of transcriptional condensates is increasingly associated with diseases, indicating a potential role in pathogenesis. In this mini-review, we provide a concise overview of the current understanding of the formation and function of transcriptional condensates, with a specific focus on recent advances in their dysregulation and implications in diseases, notably cancer. We also address limitations in the field and highlight open questions for future research.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"86 ","pages":"Article 102203"},"PeriodicalIF":4.0,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141089998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The metabolic baton: conducting the dance of N6-methyladenosine writing and erasing 代谢指挥棒：指挥 N6-甲基腺苷的书写和擦除舞蹈
IF 4 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-05-23 DOI: 10.1016/j.gde.2024.102206
Robert J. Rabelo-Fernández, Madeline Yuen, Pedro J. Batista
{"title":"The metabolic baton: conducting the dance of N6-methyladenosine writing and erasing","authors":"Robert J. Rabelo-Fernández,&nbsp;Madeline Yuen,&nbsp;Pedro J. Batista","doi":"10.1016/j.gde.2024.102206","DOIUrl":"https://doi.org/10.1016/j.gde.2024.102206","url":null,"abstract":"<div><p>The modification N6-methyladenosine (m<sup>6</sup>A) plays an important role in determining the functional output of gene expression programs. Throughout the transcriptome, the levels of m<sup>6</sup>A are tightly regulated by the opposing activities of methyltransferases and demethylases, as well as the interaction of modified transcripts with m<sup>6</sup>A-dependent RNA-binding proteins that modulate transcript stability, often referred to as writers, erasers, and readers. The enzymatic activities of both writers and erasers are tightly linked to the cellular metabolic environment, as these enzymatic reactions rely on metabolism intermediaries as cofactors. In this review, we highlight the examples of intersection between metabolism and m<sup>6</sup>A-dependent gene regulation and discuss the different contexts where this interaction plays important roles.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"86 ","pages":"Article 102206"},"PeriodicalIF":4.0,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141090118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Crosstalk between histone/DNA modifications and RNA N6-methyladenosine modification 组蛋白/DNA 修饰与 RNA N6-甲基腺苷修饰之间的相互影响
IF 4 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-05-21 DOI: 10.1016/j.gde.2024.102205
Yushuai Wang , Huilin Huang , Jianjun Chen , Hengyou Weng
{"title":"Crosstalk between histone/DNA modifications and RNA N6-methyladenosine modification","authors":"Yushuai Wang ,&nbsp;Huilin Huang ,&nbsp;Jianjun Chen ,&nbsp;Hengyou Weng","doi":"10.1016/j.gde.2024.102205","DOIUrl":"https://doi.org/10.1016/j.gde.2024.102205","url":null,"abstract":"<div><p>N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) is the most prevalent internal RNA modification in eukaryotic messenger RNAs (mRNAs), regulating gene expression at the transcription and post-transcription levels. Complex interplay between m<sup>6</sup>A and other well-studied epigenetic modifications, including histone modifications and DNA modification, has been extensively reported in recent years. The crosstalk between RNA m<sup>6</sup>A modification and histone/DNA modifications plays a critical role in establishing the chromatin state for the precise and specific fine-tuning of gene expression and undoubtedly has profound impacts on both physiological and pathological processes. In this review, we discuss the crosstalk between RNA m<sup>6</sup>A modification and histone/DNA modifications, emphasizing their sophisticated communications and the mechanisms underlying to gain a comprehensive view of the biological relevance of m<sup>6</sup>A-based epigenetic network.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"86 ","pages":"Article 102205"},"PeriodicalIF":4.0,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959437X24000546/pdfft?md5=c27e26ed84d30b55cd9e4436f1274526&pid=1-s2.0-S0959437X24000546-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141073368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring the role of ribosomal RNA modifications in cancer 探索核糖体 RNA 修饰在癌症中的作用。
IF 4 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-05-17 DOI: 10.1016/j.gde.2024.102204
Judith López , Sandra Blanco
{"title":"Exploring the role of ribosomal RNA modifications in cancer","authors":"Judith López ,&nbsp;Sandra Blanco","doi":"10.1016/j.gde.2024.102204","DOIUrl":"10.1016/j.gde.2024.102204","url":null,"abstract":"<div><p>Recent advances have highlighted the significant roles of post-transcriptional modifications in rRNA in various cancers. Evidence suggests that dysregulation of rRNA modifications acts as a common denominator in cancer development, with alterations in these modifications conferring competitive advantages to cancer cells. Specifically, rRNA modifications modulate protein synthesis and favor the specialized translation of oncogenic programs, thereby contributing to the formation of a protumorigenic proteome in cancer cells. These findings reveal a novel regulatory layer mediated by changes in the deposition of rRNA chemical modifications. Moreover, inhibition of these modifications <em>in vitro</em> and in preclinical studies demonstrates potential therapeutic applications. The recurrence of altered rRNA modification patterns across different types of cancer underscores their importance in cancer progression, proposing them as potential biomarkers and novel therapeutic targets. This review will highlight the latest insights into how post-transcriptional rRNA modifications contribute to cancer progression and summarize the main developments and ongoing challenges in this research area.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"86 ","pages":"Article 102204"},"PeriodicalIF":4.0,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959437X24000534/pdfft?md5=9866146582501a3eab86a511792a0b43&pid=1-s2.0-S0959437X24000534-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140968791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Insights into multilevel spatial regulation within the root stem cell niche 对根干细胞生态位内多层次空间调控的见解
IF 4 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-05-04 DOI: 10.1016/j.gde.2024.102200
Jessica Pérez-Sancho , Lisa Van den Broeck , Pedro García-Caparros , Rosangela Sozzani
{"title":"Insights into multilevel spatial regulation within the root stem cell niche","authors":"Jessica Pérez-Sancho ,&nbsp;Lisa Van den Broeck ,&nbsp;Pedro García-Caparros ,&nbsp;Rosangela Sozzani","doi":"10.1016/j.gde.2024.102200","DOIUrl":"https://doi.org/10.1016/j.gde.2024.102200","url":null,"abstract":"<div><p>All differentiated root cells derive from stem cells spatially organized within the stem cell niche (SCN), a microenvironment located within the root tip. Here, we compiled recent advances in the understanding of how the SCN drives the establishment and maintenance of cell types. The quiescent center (QC) is widely recognized as the primary driver of cell fate determination, but it is recently considered a convergence center of multiple signals. Cell identity of the cortex endodermis initials is mainly driven by the regulatory feedback loops between transcription factors (TFs), acting as mobile signals between neighboring cells, including the QC. As exemplified in the vascular initials, the precise spatial expression of these regulatory TFs is connected with a dynamic hormonal interplay. Thus, stem cell maintenance and cell differentiation are regulated by a plethora of signals forming a complex, multilevel regulatory network. Integrating the transcriptional and post-translational regulations, protein–protein interactions, and mobile signals into models will be fundamental for the comprehensive understanding of SCN maintenance and differentiation.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"86 ","pages":"Article 102200"},"PeriodicalIF":4.0,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140822451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Timing and Tempo in Development 发展中的时间和节奏
IF 4 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-05-03 DOI: 10.1016/j.gde.2024.102202
Miki Ebisuya , James Briscoe
{"title":"Timing and Tempo in Development","authors":"Miki Ebisuya ,&nbsp;James Briscoe","doi":"10.1016/j.gde.2024.102202","DOIUrl":"https://doi.org/10.1016/j.gde.2024.102202","url":null,"abstract":"","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"86 ","pages":"Article 102202"},"PeriodicalIF":4.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140822450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Phase separation and inheritance of repressive chromatin domains 抑制性染色质结构域的相分离与遗传
IF 4 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-05-02 DOI: 10.1016/j.gde.2024.102201
Nazli Akilli , Thierry Cheutin, Giacomo Cavalli
{"title":"Phase separation and inheritance of repressive chromatin domains","authors":"Nazli Akilli ,&nbsp;Thierry Cheutin,&nbsp;Giacomo Cavalli","doi":"10.1016/j.gde.2024.102201","DOIUrl":"https://doi.org/10.1016/j.gde.2024.102201","url":null,"abstract":"<div><p>Polycomb-associated chromatin and pericentromeric heterochromatin form genomic domains important for the epigenetic regulation of gene expression. Both Polycomb complexes and heterochromatin factors rely on ‘read and write’ mechanisms, which, on their own, are not sufficient to explain the formation and the maintenance of these epigenetic domains. Microscopy has revealed that they form specific nuclear compartments separated from the rest of the genome. Recently, some subunits of these molecular machineries have been shown to undergo phase separation, both <em>in vitro</em> and <em>in vivo</em>, suggesting that phase separation might play important roles in the formation and the function of these two kinds of repressive chromatin. In this review, we will present the recent advances in the field of facultative and constitutive heterochromatin formation and maintenance through phase separation.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"86 ","pages":"Article 102201"},"PeriodicalIF":4.0,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959437X24000509/pdfft?md5=8032b4757ed1be5a1736651db8d7a3b1&pid=1-s2.0-S0959437X24000509-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140820118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
m6A regulates heterochromatin in mammalian embryonic stem cells m6A 调节哺乳动物胚胎干细胞中的异染色质
IF 4 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-04-25 DOI: 10.1016/j.gde.2024.102196
Wenqi Xu, Hongjie Shen
{"title":"m6A regulates heterochromatin in mammalian embryonic stem cells","authors":"Wenqi Xu,&nbsp;Hongjie Shen","doi":"10.1016/j.gde.2024.102196","DOIUrl":"https://doi.org/10.1016/j.gde.2024.102196","url":null,"abstract":"<div><p>As the most well-studied modification in mRNA, m<sup>6</sup>A has been shown to regulate multiple biological processes, including RNA degradation, processing, and translation. Recent studies showed that m<sup>6</sup>A modification is enriched in chromatin-associated RNAs and nascent RNAs, suggesting m<sup>6</sup>A might play regulatory roles in chromatin contexts. Indeed, in the past several years, a number of studies have clarified how m<sup>6</sup>A and its modulators regulate different types of chromatin states. Specifically, in the past 2–3 years, several studies discovered the roles of m<sup>6</sup>A and/or its modulators in regulating constitutive and facultative heterochromatin, shedding interesting lights on RNA-dependent heterochromatin formation in mammalian cells. This review will summarize and discuss the mechanisms underlying m<sup>6</sup>A’s regulation in different types of heterochromatin, with a specific emphasis on the regulation in mammalian embryonic stem cells, which exhibit distinct features of multiple heterochromatin marks.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"86 ","pages":"Article 102196"},"PeriodicalIF":4.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140647173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hijacked enhancer–promoter and silencer–promoter loops in cancer 癌症中被劫持的增强子-启动子和沉默子-启动子环路
IF 4 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-04-25 DOI: 10.1016/j.gde.2024.102199
Xiaotao Wang , Feng Yue
{"title":"Hijacked enhancer–promoter and silencer–promoter loops in cancer","authors":"Xiaotao Wang ,&nbsp;Feng Yue","doi":"10.1016/j.gde.2024.102199","DOIUrl":"https://doi.org/10.1016/j.gde.2024.102199","url":null,"abstract":"<div><p>Recent work has shown that besides inducing fusion genes, structural variations (SVs) can also contribute to oncogenesis by disrupting the three-dimensional genome organization and dysregulating gene expression. At the chromatin-loop level, SVs can relocate enhancers or silencers from their original genomic loci to activate oncogenes or repress tumor suppressor genes. On a larger scale, different types of alterations in topologically associating domains (TADs) have been reported in cancer, such as TAD expansion, shuffling, and SV-induced neo-TADs. Furthermore, the transformation from normal cells to cancerous cells is usually coupled with active or repressive compartmental switches, and cancer-specific compartments have been proposed. This review discusses the sites, and the other latest advances in studying how SVs disrupt higher-order genome structure in cancer, which in turn leads to oncogene dysregulation. We also highlight the clinical implications of these changes and the challenges ahead in this field.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"86 ","pages":"Article 102199"},"PeriodicalIF":4.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140647172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Spatial orchestration of the genome: topological reorganisation during X-chromosome inactivation 基因组的空间协调：X 染色体失活过程中的拓扑重组
IF 4 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-04-24 DOI: 10.1016/j.gde.2024.102198
Alexandra Martitz , Edda G Schulz
{"title":"Spatial orchestration of the genome: topological reorganisation during X-chromosome inactivation","authors":"Alexandra Martitz ,&nbsp;Edda G Schulz","doi":"10.1016/j.gde.2024.102198","DOIUrl":"https://doi.org/10.1016/j.gde.2024.102198","url":null,"abstract":"<div><p>Genomes are organised through hierarchical structures, ranging from local kilobase-scale <em>cis</em>-regulatory contacts to large chromosome territories. Most notably, (sub)-compartments partition chromosomes according to transcriptional activity, while topologically associating domains (TADs) define <em>cis</em>-regulatory landscapes. The inactive X chromosome in mammals has provided unique insights into the regulation and function of the three-dimensional (3D) genome. Concurrent with silencing of the majority of genes and major alterations of its chromatin state, the X chromosome undergoes profound spatial rearrangements at multiple scales. These include the emergence of megadomains, alterations of the compartment structure and loss of the majority of TADs. Moreover, the <em>Xist</em> locus, which orchestrates X-chromosome inactivation, has provided key insights into regulation and function of regulatory domains. This review provides an overview of recent insights into the control of these structural rearrangements and contextualises them within a broader understanding of 3D genome organisation.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"86 ","pages":"Article 102198"},"PeriodicalIF":4.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959437X24000479/pdfft?md5=dcd903d7883bdadf5306e5917272da42&pid=1-s2.0-S0959437X24000479-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140643634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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