Pub Date : 2023-12-20DOI: 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.
{"title":"Exploring new roles for RNA-binding proteins in epigenetic and gene regulation","authors":"Pedro Avila-Lopez , Shannon M Lauberth","doi":"10.1016/j.gde.2023.102136","DOIUrl":"10.1016/j.gde.2023.102136","url":null,"abstract":"<div><p><span>A significant portion of the human proteome comprises RNA-binding proteins (RBPs) that play fundamental roles in numerous </span>biological processes<span><span>. 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 </span>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.</span></p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138832830","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}
Pub Date : 2023-12-12DOI: 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.
{"title":"Polycomb repressive complex 2 accessory factors: rheostats for cell fate decision?","authors":"Hina Bharti , Sungwook Han , Han-Wen Chang , Danny Reinberg","doi":"10.1016/j.gde.2023.102137","DOIUrl":"10.1016/j.gde.2023.102137","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959437X2300117X/pdfft?md5=c90607690ced8c29da1feecf9cf354e3&pid=1-s2.0-S0959437X2300117X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138576205","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}
Pub Date : 2023-12-05DOI: 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.
{"title":"Topical section: embryonic models (2023) for Current Opinion in Genetics & Development","authors":"Charlotte E Handford , Sergi Junyent , Victoria Jorgensen , Magdalena Zernicka-Goetz","doi":"10.1016/j.gde.2023.102134","DOIUrl":"10.1016/j.gde.2023.102134","url":null,"abstract":"<div><p><span>Stem cell-based mammalian embryo models facilitate the discovery of developmental mechanisms because they are more amenable to genetic<span> and epigenetic perturbations than natural embryos. Here, we highlight exciting recent advances that have yielded a plethora of models of </span></span>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.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138488971","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}
Pub Date : 2023-12-04DOI: 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.
{"title":"Human blastoid as an in vitro model of human blastocysts","authors":"Xiaodong Liu , Jose M Polo","doi":"10.1016/j.gde.2023.102135","DOIUrl":"10.1016/j.gde.2023.102135","url":null,"abstract":"<div><p>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 <em>in vitro</em> 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.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959437X23001156/pdfft?md5=9a6eae3b487a1baccf0554d4dd293f3a&pid=1-s2.0-S0959437X23001156-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138488970","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}
Pub Date : 2023-12-01DOI: 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.
{"title":"New perspectives on the causes and consequences of male meiotic drive","authors":"Cécile Courret , Xiaolu Wei , Amanda M Larracuente","doi":"10.1016/j.gde.2023.102111","DOIUrl":"10.1016/j.gde.2023.102111","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959437X23000916/pdfft?md5=659c68dd25b2312a2883e8a57675fc15&pid=1-s2.0-S0959437X23000916-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10231468","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}
Pub Date : 2023-11-09DOI: 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.
{"title":"‘Enhancing’ skeletal muscle and stem cells in three-dimensional: genome regulation of skeletal muscle in development and disease","authors":"Matthew A. Romero , April D. Pyle","doi":"10.1016/j.gde.2023.102133","DOIUrl":"10.1016/j.gde.2023.102133","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89720394","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}
Pub Date : 2023-11-04DOI: 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.
{"title":"Somatic mutation burden in relation to aging and functional life span: implications for cellular reprogramming and rejuvenation","authors":"Alexander Y Maslov , Jan Vijg","doi":"10.1016/j.gde.2023.102132","DOIUrl":"10.1016/j.gde.2023.102132","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71488386","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}
Pub Date : 2023-10-26DOI: 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.
{"title":"Modifying gastruloids to dissect mechanisms of tissue-specific induction","authors":"David A Turner , Jennifer Nichols","doi":"10.1016/j.gde.2023.102130","DOIUrl":"10.1016/j.gde.2023.102130","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959437X23001107/pdfft?md5=e52f798931d6c64ed8d544500915e07b&pid=1-s2.0-S0959437X23001107-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66784547","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}
Pub Date : 2023-10-20DOI: 10.1016/j.gde.2023.102131
Harmit S Malik, Judith E Mank
{"title":"Editorial overview: Conflicts, conflicts everywhere","authors":"Harmit S Malik, Judith E Mank","doi":"10.1016/j.gde.2023.102131","DOIUrl":"10.1016/j.gde.2023.102131","url":null,"abstract":"","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49693553","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}
Pub Date : 2023-10-20DOI: 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.
{"title":"Divergent outcomes of genetic conflict on the UV sex chromosomes of Marchantia polymorpha and Ceratodon purpureus","authors":"Stuart F McDaniel","doi":"10.1016/j.gde.2023.102129","DOIUrl":"10.1016/j.gde.2023.102129","url":null,"abstract":"<div><p>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 <em>Marchantia polymorpha</em> and <em>Ceratodon purpureus</em> 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, <em>M. polymorpha</em> relies on biased autosomal expression, while in <em>C. purpureus</em>, 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.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49684495","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}