{"title":"Editorial overview: Epitranscriptomics: Exploring a new frontier in health and disease","authors":"François Fuks , Michael Kharas","doi":"10.1016/j.gde.2024.102271","DOIUrl":"10.1016/j.gde.2024.102271","url":null,"abstract":"","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"89 ","pages":"Article 102271"},"PeriodicalIF":3.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512329","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}
{"title":"Emerging interactions between RNA methylation and chromatin architecture","authors":"Amber Louwagie , Ly P Vu","doi":"10.1016/j.gde.2024.102270","DOIUrl":"10.1016/j.gde.2024.102270","url":null,"abstract":"<div><div>Epitranscriptomics, the study of chemical modifications of RNA molecules, is increasingly recognized as an important component of gene expression regulation. While the majority of research has focused on N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) RNA methylation on mRNAs, emerging evidence has revealed that the m<sup>6</sup>A modification extends beyond mRNAs to include chromatin-associated RNAs (caRNAs). CaRNAs constitute an important class of RNAs characterized by their interaction with the genome and epigenome. These features allow caRNAs to be actively involved in shaping genome organization. In this review, we bring into focus recent findings of the dynamic interactions between caRNAs and chromatin architecture and how RNA methylation impacts caRNAs’ function in this interplay. We highlight several enabling techniques, which were critical for genome-wide profiling of caRNAs and their modifications. Given the nascent stage of the field, we emphasize on the need to address critical gaps in study of these modifications in more relevant biological systems. Overall, these exciting progress have expanded the scope and reach of epitranscriptomics, unveiling new mechanisms that underpin the control of gene expression and cellular phenotypes, with potential therapeutic implications.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"89 ","pages":"Article 102270"},"PeriodicalIF":3.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445597","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}
{"title":"Genome folding and zygotic genome activation in mammalian preimplantation embryos","authors":"Anastasiia Bondarieva, Kikuë Tachibana","doi":"10.1016/j.gde.2024.102268","DOIUrl":"10.1016/j.gde.2024.102268","url":null,"abstract":"<div><div>The totipotent one-cell embryo, or zygote, gives rise to all germ layers and extraembryonic tissues that culminate in the development of a new organism. A zygote is produced at fertilisation by the fusion of differentiated germ cells, egg and sperm. The chromatin of parental genomes is reprogrammed and spatially reorganised in the early embryo. The 3D chromatin organisation is established <em>de novo</em> after fertilisation by a cohesin-dependent mechanism of loop extrusion that forms chromatin loops and topologically associating domains (TADs). Strengthening of TAD insulation is concomitant with the transcriptional ‘awakening’ of the embryo known as zygotic genome activation (ZGA). Whether and how these processes are causally linked remains poorly understood. In this review, we discuss recent findings of 3D chromatin organisation in mammalian gametes and embryos and how these are potentially related to ZGA.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"89 ","pages":"Article 102268"},"PeriodicalIF":3.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394940","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}
{"title":"Human-specific genetic hallmarks in neocortical development: focus on neural progenitors","authors":"Lidiia Tynianskaia , Michael Heide","doi":"10.1016/j.gde.2024.102267","DOIUrl":"10.1016/j.gde.2024.102267","url":null,"abstract":"<div><div>The evolutionary expansion of the neocortex in the ape lineage is the basis for the development of higher cognitive abilities. However, the human brain has uniquely increased in size and degree of folding, forming an essential foundation for advanced cognitive functions. This raises the question: what factors distinguish humans from our closest living primate relatives, such as chimpanzees and bonobos, which exhibit comparatively constrained cognitive capabilities? In this review, we focus on recent studies examining (modern) human-specific genetic traits that influence neural progenitor cells, whose behavior and activity are crucial for shaping cortical morphology. We emphasize the role of human-specific genetic modifications in signaling pathways that enhance the abundance of apical and basal progenitors, as well as the importance of basal progenitor metabolism in their proliferation in human. Additionally, we discuss how changes in neuron morphology contribute to the evolution of human cognition and provide our perspective on future directions in the field.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"89 ","pages":"Article 102267"},"PeriodicalIF":3.7,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394941","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}
{"title":"The power of proximity: mechanisms and biological roles of transvection","authors":"Benjamin Prud’homme","doi":"10.1016/j.gde.2024.102269","DOIUrl":"10.1016/j.gde.2024.102269","url":null,"abstract":"<div><div>The phenomenon of transvection, defined as a proximity-dependent interallelic interaction, has been observed in the context of complementation between mutant alleles for numerous Drosophila genes. Cases of transvection-like phenomena have also been observed in other species, including mammals. However, the potential contribution of transvection to wild-type gene regulation and the underlying mechanisms remain uncertain. Here, I review recent evidence demonstrating the relevance of transvection in physiological contexts. These findings suggest that transvection represents an additional layer of gene regulation that allows cells to fine-tune gene expression based on the proximity of homologous alleles. In addition, recent studies have measured the physical distance between interacting alleles, revealing unexpectedly large and variable distances. I will discuss how these distances are compatible with the ‘hub’ model of transcriptional regulation.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"89 ","pages":"Article 102269"},"PeriodicalIF":3.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378517","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}
Baptiste Libé-Philippot , Franck Polleux , Pierre Vanderhaeghen
{"title":"If you please, draw me a neuron — linking evolutionary tinkering with human neuron evolution","authors":"Baptiste Libé-Philippot , Franck Polleux , Pierre Vanderhaeghen","doi":"10.1016/j.gde.2024.102260","DOIUrl":"10.1016/j.gde.2024.102260","url":null,"abstract":"<div><div>Animal speciation often involves novel behavioral features that rely on nervous system evolution. Human-specific brain features have been proposed to underlie specialized cognitive functions and to be linked, at least in part, to the evolution of synapses, neurons, and circuits of the cerebral cortex. Here, we review recent results showing that, while the human cortex is composed of a repertoire of cells that appears to be largely similar to the one found in other mammals, human cortical neurons do display specialized features at many levels, from gene expression to intrinsic physiological properties. The molecular mechanisms underlying human species-specific neuronal features remain largely unknown but implicate hominid-specific gene duplicates that encode novel molecular modifiers of neuronal function. The identification of human-specific genetic modifiers of neuronal function brings novel insights on brain evolution and function and, could also provide new insights on human species-specific vulnerabilities to brain disorders.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"89 ","pages":"Article 102260"},"PeriodicalIF":3.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367300","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}
{"title":"Reconstructing human-specific regulatory functions in model systems","authors":"Marybeth Baumgartner , Yu Ji , James P Noonan","doi":"10.1016/j.gde.2024.102259","DOIUrl":"10.1016/j.gde.2024.102259","url":null,"abstract":"<div><p>Uniquely human physical traits, such as an expanded cerebral cortex and changes in limb morphology that allow us to use tools and walk upright, are in part due to human-specific genetic changes that altered when, where, and how genes are expressed during development. Over 20 000 putative regulatory elements with potential human-specific functions have been discovered. Understanding how these elements contributed to human evolution requires identifying candidates most likely to have shaped human traits, then studying them in genetically modified animal models. Here, we review the progress and challenges in generating and studying such models and propose a pathway for advancing the field. Finally, we highlight that large-scale collaborations across multiple research domains are essential to decipher what makes us human.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"89 ","pages":"Article 102259"},"PeriodicalIF":3.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142171834","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}
{"title":"Molecular mechanisms of the specialization of human synapses in the neocortex","authors":"Eirini Christopoulou, Cécile Charrier","doi":"10.1016/j.gde.2024.102258","DOIUrl":"10.1016/j.gde.2024.102258","url":null,"abstract":"<div><p>Synapses of the neocortex specialized during human evolution to develop over extended timescales, process vast amounts of information and increase connectivity, which is thought to underlie our advanced social and cognitive abilities. These features reflect species-specific regulations of neuron and synapse cell biology. However, despite growing understanding of the human genome and the brain transcriptome at the single-cell level, linking human-specific genetic changes to the specialization of human synapses has remained experimentally challenging. In this review, we describe recent progress in characterizing divergent morphofunctional and developmental properties of human synapses, and we discuss new insights into the underlying molecular mechanisms. We also highlight intersections between evolutionary innovations and disorder-related dysfunctions at the synapse.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"89 ","pages":"Article 102258"},"PeriodicalIF":3.7,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959437X24001072/pdfft?md5=ef039913beee7944234497d1dfe20f66&pid=1-s2.0-S0959437X24001072-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142164826","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}
{"title":"Exploiting the plasticity of cholangiocytes to repair the biliary tree","authors":"Carla Frau , Ludovic Vallier","doi":"10.1016/j.gde.2024.102257","DOIUrl":"10.1016/j.gde.2024.102257","url":null,"abstract":"<div><p>Cholangiocytes are the main cell type lining the epithelium of the biliary tree of the liver. This cell type has been implicated not only in diseases affecting the biliary tree but also in chronic liver diseases targeting other hepatic cells such as hepatocytes. However, the isolation and culture of cholangiocytes have been particularly arduous, thereby limiting the development of new therapies. The emergence of organoids has the potential to address in part this challenge. Indeed, cholangiocyte organoids can be established from both the intra- and extrahepatic regions of the biliary tree, providing an advantageous platform for disease modeling and mechanism investigations. Accordingly, recent studies on cholangiocyte organoids, together with the advent of single-cell -omics, have opened the field to exciting discoveries concerning the plastic nature of these cells and their capability to adapt to different environments and stimuli. This review will focus on describing how these plasticity properties could be exploited in regenerative medicine and cell-based therapy, opening new frontiers for treating disorders affecting the biliary tree and beyond.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"89 ","pages":"Article 102257"},"PeriodicalIF":3.7,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959437X24001060/pdfft?md5=9e6c6420fd11cc3e263f24c031cdf99d&pid=1-s2.0-S0959437X24001060-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142164765","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}
{"title":"Editorial overview: Breaking boundaries: new frontiers in chromatin regulation for cancer therapy","authors":"Ali Shilatifard, Shannon M Lauberth","doi":"10.1016/j.gde.2024.102255","DOIUrl":"10.1016/j.gde.2024.102255","url":null,"abstract":"","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"88 ","pages":"Article 102255"},"PeriodicalIF":3.7,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142128245","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}