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Inheritance of epigenetic transcriptional memory 表观遗传转录记忆的遗传
IF 4 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-03-01 DOI: 10.1016/j.gde.2024.102174
Tiffany Ge, Jason H Brickner
{"title":"Inheritance of epigenetic transcriptional memory","authors":"Tiffany Ge,&nbsp;Jason H Brickner","doi":"10.1016/j.gde.2024.102174","DOIUrl":"https://doi.org/10.1016/j.gde.2024.102174","url":null,"abstract":"<div><p>Epigenetic memory allows organisms to stably alter their transcriptional program in response to developmental or environmental stimuli. Such transcriptional programs are mediated by heritable regulation of the function of enhancers and promoters. Memory involves read–write systems that enable self-propagation and mitotic inheritance of <em>cis-</em>acting epigenetic marks to induce stable changes in transcription. Also, in response to environmental cues, cells can induce epigenetic transcriptional memory to poise inducible genes for faster induction in the future. Here, we discuss modes of epigenetic inheritance and the molecular basis of epigenetic transcriptional memory.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"85 ","pages":"Article 102174"},"PeriodicalIF":4.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139998999","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
Somatic hypermutation mechanisms during lymphomagenesis and transformation 淋巴瘤发生和转化过程中的体细胞超突变机制
IF 4 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-02-29 DOI: 10.1016/j.gde.2024.102165
Max C Lauring , Uttiya Basu
{"title":"Somatic hypermutation mechanisms during lymphomagenesis and transformation","authors":"Max C Lauring ,&nbsp;Uttiya Basu","doi":"10.1016/j.gde.2024.102165","DOIUrl":"https://doi.org/10.1016/j.gde.2024.102165","url":null,"abstract":"<div><p>B cells undergoing physiologically programmed or aberrant genomic alterations provide an opportune system to study the causes and consequences of genome mutagenesis. Activated B cells in germinal centers express activation-induced cytidine deaminase (AID) to accomplish physiological somatic hypermutation (SHM) of their antibody-encoding genes. In attempting to diversify their immunoglobulin (Ig) heavy- and light-chain genes, several B-cell clones successfully optimize their antigen-binding affinities. However, SHM can sometimes occur at non-Ig loci, causing genetic alternations that lay the foundation for lymphomagenesis, particularly diffuse large B-cell lymphoma. Thus, SHM acts as a double-edged sword, bestowing superb humoral immunity at the potential risk of initiating disease. We refer to off-target, non-Ig AID mutations — that are often but not always associated with disease — as aberrant SHM (aSHM). A key challenge in understanding SHM and aSHM is determining how AID targets and mutates specific DNA sequences in the Ig loci to generate antibody diversity and non-Ig genes to initiate lymphomagenesis. Herein, we discuss some current advances regarding the regulation of AID’s DNA mutagenesis activity in B cells.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"85 ","pages":"Article 102165"},"PeriodicalIF":4.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139999877","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 influencers' era: how the environment shapes chromatin in 3D 影响者时代：环境如何塑造三维染色质
IF 4 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-02-28 DOI: 10.1016/j.gde.2024.102173
Lorenz Pudelko , Daphne S Cabianca
{"title":"The influencers' era: how the environment shapes chromatin in 3D","authors":"Lorenz Pudelko ,&nbsp;Daphne S Cabianca","doi":"10.1016/j.gde.2024.102173","DOIUrl":"https://doi.org/10.1016/j.gde.2024.102173","url":null,"abstract":"<div><p>Environment–epigenome interactions are emerging as contributors to disease risk and health outcomes. In fact, organisms outside of the laboratory are constantly exposed to environmental changes that can influence chromatin regulation at multiple levels, potentially impacting on genome function. In this review, we will summarize recent findings on how major external cues impact on 3D chromatin organization in different experimental systems. We will describe environment-induced 3D genome alterations ranging from chromatin accessibility to the spatial distribution of the genome and discuss their role in regulating gene expression.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"85 ","pages":"Article 102173"},"PeriodicalIF":4.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959437X24000224/pdfft?md5=be6b6be1e4ca4b6506f001e7bacffb77&pid=1-s2.0-S0959437X24000224-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139986857","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
Editorial overview: Early embryonic development models: back to the beginning 编辑综述：早期胚胎发育模型：回到起点
IF 4 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-02-27 DOI: 10.1016/j.gde.2024.102175
Miguel A Esteban, Jose M Polo
{"title":"Editorial overview: Early embryonic development models: back to the beginning","authors":"Miguel A Esteban,&nbsp;Jose M Polo","doi":"10.1016/j.gde.2024.102175","DOIUrl":"https://doi.org/10.1016/j.gde.2024.102175","url":null,"abstract":"","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"85 ","pages":"Article 102175"},"PeriodicalIF":4.0,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139986212","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
Epigenetic control and manipulation of neuronal maturation timing 表观遗传学控制和操纵神经元的成熟时间。
IF 4 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-02-27 DOI: 10.1016/j.gde.2024.102164
Gabriele Ciceri , Lorenz Studer
{"title":"Epigenetic control and manipulation of neuronal maturation timing","authors":"Gabriele Ciceri ,&nbsp;Lorenz Studer","doi":"10.1016/j.gde.2024.102164","DOIUrl":"10.1016/j.gde.2024.102164","url":null,"abstract":"<div><p>During brain development, the sequence of developmental steps and the underlying transcriptional regulatory logic are largely conserved across species. However, the temporal unfolding of developmental programs varies dramatically across species and within a given species varies across brain regions and cell identities. The maturation of neurons in the human cerebral cortex is particularly slow and lasts for many years compared with only a few weeks for the corresponding mouse neurons. The mechanisms setting the ‘schedule’ of neuronal maturation remain unclear but appear to be linked to a cell-intrinsic ‘clock’. Here, we discuss recent findings that highlight a role for epigenetic factors in the timing of neuronal maturation. Manipulations of those factors in stem cell-based models can override the intrinsic pace of neuronal maturation, including its protracted nature in human cortical neurons. We then contextualize the epigenetic regulation of maturation programs with findings from other model systems and propose potential interactions between epigenetic pathways and other drivers of developmental rates.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"85 ","pages":"Article 102164"},"PeriodicalIF":4.0,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959437X24000133/pdfft?md5=b98dfb5ec4b409ad7692d5e9f604f834&pid=1-s2.0-S0959437X24000133-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139984396","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
Approaches to probe and perturb long noncoding RNA functions in diseases 探究和扰乱疾病中长非编码 RNA 功能的方法。
IF 4 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-02-26 DOI: 10.1016/j.gde.2024.102158
Guiping Wang , Yannick Lee-Yow , Howard Y Chang
{"title":"Approaches to probe and perturb long noncoding RNA functions in diseases","authors":"Guiping Wang ,&nbsp;Yannick Lee-Yow ,&nbsp;Howard Y Chang","doi":"10.1016/j.gde.2024.102158","DOIUrl":"10.1016/j.gde.2024.102158","url":null,"abstract":"<div><p>Long noncoding RNAs (lncRNAs) are a class of RNA molecules exceeding 200 nucleotides in length that lack long open-reading frames. Transcribed predominantly by RNA polymerase II (&gt;500nt), lncRNAs can undergo splicing and are produced from various regions of the genome, including intergenic regions, introns, and in antisense orientation to protein-coding genes. Aberrations in lncRNA expression or function have been associated with a wide variety of diseases, including cancer, cardiovascular diseases, diabetes, and neurodegeneration. Despite the growing recognition of select lncRNAs as key players in cellular processes and diseases, several challenges obscure a comprehensive understanding of their functional landscape. Recent technological innovations, such as in sequencing, affinity-based techniques, imaging, and RNA perturbation, have advanced functional characterization and mechanistic understanding of disease-associated lncRNAs.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"85 ","pages":"Article 102158"},"PeriodicalIF":4.0,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959437X24000078/pdfft?md5=ed3ed3df1b5cae13ab73b12d03dc7ae2&pid=1-s2.0-S0959437X24000078-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139984395","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
Hexasomal particles: consequence or also consequential? 六面体微粒：结果还是后果？
IF 4 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-02-26 DOI: 10.1016/j.gde.2024.102163
Upneet Kaur , Elise N Muñoz , Geeta J Narlikar
{"title":"Hexasomal particles: consequence or also consequential?","authors":"Upneet Kaur ,&nbsp;Elise N Muñoz ,&nbsp;Geeta J Narlikar","doi":"10.1016/j.gde.2024.102163","DOIUrl":"10.1016/j.gde.2024.102163","url":null,"abstract":"<div><p>It is long known that an RNA polymerase transcribing through a nucleosome can generate subnucleosomal particles called hexasomes. These particles lack an H2A–H2B dimer, breaking the symmetry of a nucleosome and revealing new interfaces. Whether hexasomes are simply a consequence of RNA polymerase action or they also have a regulatory impact remains an open question. Recent biochemical and structural studies of RNA polymerases and chromatin remodelers with hexasomes motivated us to revisit this question. Here, we build on previous models to discuss how formation of hexasomes can allow sophisticated regulation of transcription and also significantly impact chromatin folding. We anticipate that further cellular and biochemical analysis of these subnucleosomal particles will uncover additional regulatory roles.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"85 ","pages":"Article 102163"},"PeriodicalIF":4.0,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139984397","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
Therapeutic index of targeting select chromatin complexes in human cancer patients 针对人类癌症患者选定染色质复合物的治疗指数
IF 4 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-02-24 DOI: 10.1016/j.gde.2024.102162
Yuan Gao , Christopher R Vakoc
{"title":"Therapeutic index of targeting select chromatin complexes in human cancer patients","authors":"Yuan Gao ,&nbsp;Christopher R Vakoc","doi":"10.1016/j.gde.2024.102162","DOIUrl":"https://doi.org/10.1016/j.gde.2024.102162","url":null,"abstract":"<div><p>Aberrant chromatin regulation can promote the initiation and progression of human cancer. An improved understanding of such mechanisms has resulted in the identification of cancers with an enhanced dependency on specific chromatin regulatory proteins relative to nonmalignant cell types. Hence, targeting of such complexes with small molecules has significant therapeutic potential in oncology. In recent years, several drugs have been developed and evaluated in human cancer patients, which can influence tumor biology by reprogramming of chromatin structure. In this review, we summarize several of the known mechanisms that endow cancer cells with a powerful dependency on chromatin regulation that exceeds the requirements for normal tissue homeostasis. We also summarize the remarkable small-molecule inhibitors that exploit chromatin regulator dependencies with a clear therapeutic benefit in human cancer patients.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"85 ","pages":"Article 102162"},"PeriodicalIF":4.0,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139942297","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
Cohesin regulation and roles in chromosome structure and function 凝聚素在染色体结构和功能中的调控和作用
IF 4 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-02-20 DOI: 10.1016/j.gde.2024.102159
Natalie L Rittenhouse , Jill M Dowen
{"title":"Cohesin regulation and roles in chromosome structure and function","authors":"Natalie L Rittenhouse ,&nbsp;Jill M Dowen","doi":"10.1016/j.gde.2024.102159","DOIUrl":"https://doi.org/10.1016/j.gde.2024.102159","url":null,"abstract":"<div><p>Chromosome structure regulates DNA-templated processes such as transcription of genes. Dynamic changes to chromosome structure occur during development and in disease contexts. The cohesin complex is a molecular motor that regulates chromosome structure by generating DNA loops that bring two distal genomic sites into close spatial proximity. There are many open questions regarding the formation and dissolution of DNA loops, as well as the role(s) of DNA loops in regulating transcription of the interphase genome. This review focuses on recent discoveries that provide molecular insights into the role of cohesin and chromosome structure in gene transcription during development and disease.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"85 ","pages":"Article 102159"},"PeriodicalIF":4.0,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959437X2400008X/pdfft?md5=215847571452c414787e0e250eae0318&pid=1-s2.0-S0959437X2400008X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139907976","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
A CTCF-dependent mechanism underlies the Hox timer: relation to a segmented body plan 依赖于 CTCF 的机制是 Hox 定时器的基础：与分节身体计划的关系
IF 4 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-02-19 DOI: 10.1016/j.gde.2024.102160
Hocine Rekaik , Denis Duboule
{"title":"A CTCF-dependent mechanism underlies the Hox timer: relation to a segmented body plan","authors":"Hocine Rekaik ,&nbsp;Denis Duboule","doi":"10.1016/j.gde.2024.102160","DOIUrl":"https://doi.org/10.1016/j.gde.2024.102160","url":null,"abstract":"<div><p>During gastrulation, Hox genes are activated in a time-sequence that follows the order of the genes along their clusters. This property, which is observed in all animals that develop following a progressive rostral-to-caudal morphogenesis, is associated with changes in the chromatin structure and epigenetic profiles of Hox clusters, suggesting a process at least partly based on sequential gene accessibility. Here, we discuss recent work on this issue, as well as a possible mechanism based on the surprising conservation in both the distribution and orientation of CTCF sites inside vertebrate Hox clusters.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"85 ","pages":"Article 102160"},"PeriodicalIF":4.0,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959437X24000091/pdfft?md5=6fe54b1cc0c700d54e224e4ee72d8ffc&pid=1-s2.0-S0959437X24000091-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139901246","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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