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- Volume 49, 2015
Annual Review of Genetics - Volume 49, 2015
Volume 49, 2015
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Brachypodium distachyon as a Genetic Model System
Vol. 49 (2015), pp. 1–20More LessBrachypodium distachyon has emerged as a powerful model system for studying the genetics of flowering plants. Originally chosen for its phylogenetic proximity to the large-genome cereal crops wheat and barley, it is proving to be useful for more than simply providing markers for comparative mapping. Studies in B. distachyon have provided new insight into the structure and physiology of plant cell walls, the development and chemical composition of endosperm, and the genetic basis for cold tolerance. Recent work on auxin transport has uncovered mechanisms that apply to all angiosperms other than Arabidopsis. In addition to the areas in which it is currently used, B. distachyon is uniquely suited for studies of floral development, vein patterning, the controls of the perennial versus annual habit, and genome organization.
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Genetic Dissection of the Host Tropism of Human-Tropic Pathogens
Vol. 49 (2015), pp. 21–45More LessInfectious diseases are the second leading cause of death worldwide. Although the host multitropism of some pathogens has rendered their manipulation possible in animal models, the human-restricted tropism of numerous viruses, bacteria, fungi, and parasites has seriously hampered our understanding of these pathogens. Hence, uncovering the genetic basis underlying the narrow tropism of such pathogens is critical for understanding their mechanisms of infection and pathogenesis. Moreover, such genetic dissection is essential for the generation of permissive animal models that can serve as critical tools for the development of therapeutics or vaccines against challenging human pathogens. In this review, we describe different experimental approaches utilized to uncover the genetic foundation regulating pathogen host tropism as well as their relevance for studying the tropism of several important human pathogens. Finally, we discuss the current and future uses of this knowledge for generating genetically modified animal models permissive for these pathogens.
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From Genomics to Gene Therapy: Induced Pluripotent Stem Cells Meet Genome Editing
Vol. 49 (2015), pp. 47–70More LessThe advent of induced pluripotent stem (iPS) cells has opened up numerous avenues of opportunity for cell therapy, including the initiation in September 2014 of the first human clinical trial to treat dry age-related macular degeneration. In parallel, advances in genome-editing technologies by site-specific nucleases have dramatically improved our ability to edit endogenous genomic sequences at targeted sites of interest. In fact, clinical trials have already begun to implement this technology to control HIV infection. Genome editing in iPS cells is a powerful tool and enables researchers to investigate the intricacies of the human genome in a dish. In the near future, the groundwork laid by such an approach may expand the possibilities of gene therapy for treating congenital disorders. In this review, we summarize the exciting progress being made in the utilization of genomic editing technologies in pluripotent stem cells and discuss remaining challenges toward gene therapy applications.
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Engineering of Secondary Metabolism
Vol. 49 (2015), pp. 71–94More LessSecondary (specialized) metabolites, produced by bacteria, fungi, plants, and other organisms, exhibit enormous structural variation, and consequently display a wide range of biological activities. Secondary metabolism improves and modulates the phenotype of the host producer. Furthermore, these biological activities have resulted in the use of secondary metabolites in a variety of industrial and pharmaceutical applications. Metabolic engineering presents a powerful strategy to improve access to these valuable molecules. A critical overview of engineering approaches in secondary metabolism is presented, both in heterologous and native hosts. The recognition of the increasing role of compartmentalization in metabolic engineering is highlighted. Engineering approaches to modify the structure of key secondary metabolite classes are also critically evaluated.
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Centromere Associations in Meiotic Chromosome Pairing
Vol. 49 (2015), pp. 95–114More LessProduction of gametes of halved ploidy for sexual reproduction requires a specialized cell division called meiosis. The fusion of two gametes restores the original ploidy in the new generation, and meiosis thus stabilizes ploidy across generations. To ensure balanced distribution of chromosomes, pairs of homologous chromosomes (homologs) must recognize each other and pair in the first meiotic division. Recombination plays a key role in this in most studied species, but it is not the only actor and particular chromosomal regions are known to facilitate the meiotic pairing of homologs. In this review, we focus on the roles of centromeres and in particular on the clustering and pairwise associations of nonhomologous centromeres that precede stable pairing between homologs. Although details vary from species to species, it is becoming increasingly clear that these associations play active roles in the meiotic chromosome pairing process, analogous to those of the telomere bouquet.
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Chromosome-Membrane Interactions in Bacteria
Vol. 49 (2015), pp. 115–129More LessProkaryotes, by definition, do not segregate their genetic material from the cytoplasm. Thus, there is no barrier preventing direct interactions between chromosomal DNA and the plasma membrane. The possibility of such interactions in bacteria was proposed long ago and supported by early electron microscopy and cell fractionation studies. However, the identification and characterization of chromosome-membrane interactions have been slow in coming. Recently, this subject has seen more progress, driven by advances in imaging techniques and in the exploration of diverse cellular processes. A number of loci have been identified in specific bacteria that depend on interactions with the membrane for their function. In addition, there is growing support for a general mechanism of DNA-membrane contacts based on transertion—concurrent transcription, translation, and insertion of membrane proteins. This review summarizes the history and recent results of chromosome-membrane associations and discusses the known and theorized consequences of these interactions in the bacterial cell.
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Understanding Language from a Genomic Perspective
Vol. 49 (2015), pp. 131–160More LessLanguage is a defining characteristic of the human species, but its foundations remain mysterious. Heritable disorders offer a gateway into biological underpinnings, as illustrated by the discovery that FOXP2 disruptions cause a rare form of speech and language impairment. The genetic architecture underlying language-related disorders is complex, and although some progress has been made, it has proved challenging to pinpoint additional relevant genes with confidence. Next-generation sequencing and genome-wide association studies are revolutionizing understanding of the genetic bases of other neurodevelopmental disorders, like autism and schizophrenia, and providing fundamental insights into the molecular networks crucial for typical brain development. We discuss how a similar genomic perspective, brought to the investigation of language-related phenotypes, promises to yield equally informative discoveries. Moreover, we outline how follow-up studies of genetic findings using cellular systems and animal models can help to elucidate the biological mechanisms involved in the development of brain circuits supporting language.
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The History of Patenting Genetic Material
Vol. 49 (2015), pp. 161–182More LessThe US Supreme Court's recent decision in Association for Molecular Pathology v. Myriad Genetics, Inc. declared, for the first time, that isolated human genes cannot be patented. Many have wondered how genes were ever the subjects of patents. The answer lies in a nuanced understanding of both legal and scientific history. Since the early twentieth century, “products of nature” were not eligible to be patented unless they were “isolated and purified” from their surrounding environment. As molecular biology advanced, and the capability to isolate genes both physically and by sequence came to fruition, researchers (and patent offices) began to apply patent-law logic to genes themselves. These patents, along with other biological patents, generated substantial social and political criticism. Myriad Genetics, a company with patents on BRCA1 and BRCA2, two genes critical to assessing early-onset breast and ovarian cancer risk, and with a particularly controversial business approach, became the antagonist in an ultimately successful campaign to overturn gene patents in court. Despite Myriad's defeat, some questions concerning the rights to monopolize genetic information remain. The history leading to that defeat may be relevant to these future issues.
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Chromothripsis: A New Mechanism for Rapid Karyotype Evolution
Vol. 49 (2015), pp. 183–211More LessChromosomal rearrangements are generally thought to accumulate gradually over many generations. However, DNA sequencing of cancer and congenital disorders uncovered a new pattern in which multiple rearrangements arise all at once. The most striking example, chromothripsis, is characterized by tens or hundreds of rearrangements confined to a single chromosome or to local regions over a few chromosomes. Genomic analysis of chromothripsis and the search for its biological mechanism have led to new insights on how chromosome segregation errors can generate mutagenesis and changes to the karyotype. Here, we review the genomic features of chromothripsis and summarize recent progress on understanding its mechanism. This includes reviewing new work indicating that one mechanism to generate chromothripsis is through the physical isolation of chromosomes in abnormal nuclear structures (micronuclei). We also discuss connections revealed by recent genomic analysis of cancers between chromothripsis, chromosome bridges, and ring chromosomes.
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A Uniform System for the Annotation of Vertebrate microRNA Genes and the Evolution of the Human microRNAome
Vol. 49 (2015), pp. 213–242More LessAlthough microRNAs (miRNAs) are among the most intensively studied molecules of the past 20 years, determining what is and what is not a miRNA has not been straightforward. Here, we present a uniform system for the annotation and nomenclature of miRNA genes. We show that less than a third of the 1,881 human miRBase entries, and only approximately 16% of the 7,095 metazoan miRBase entries, are robustly supported as miRNA genes. Furthermore, we show that the human repertoire of miRNAs has been shaped by periods of intense miRNA innovation and that mature gene products show a very different tempo and mode of sequence evolution than star products. We establish a new open access database—MirGeneDB (http://mirgenedb.org)—to catalog this set of miRNAs, which complements the efforts of miRBase but differs from it by annotating the mature versus star products and by imposing an evolutionary hierarchy upon this curated and consistently named repertoire.
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Clusters of Multiple Mutations: Incidence and Molecular Mechanisms*
Vol. 49 (2015), pp. 243–267More LessIt has been long understood that mutation distribution is not completely random across genomic space and in time. Indeed, recent surprising discoveries identified multiple simultaneous mutations occurring in tiny regions within chromosomes while the rest of the genome remains relatively mutation-free. Mechanistic elucidation of these phenomena, called mutation showers, mutation clusters, or kataegis, in parallel with findings of abundant clustered mutagenesis in cancer genomes, is ongoing. So far, the combination of factors most important for clustered mutagenesis is the induction of DNA lesions within unusually long and persistent single-strand DNA intermediates. In addition to being a fascinating phenomenon, clustered mutagenesis also became an indispensable tool for identifying a previously unrecognized major source of mutation in cancer, APOBEC cytidine deaminases. Future research on clustered mutagenesis may shed light onto important mechanistic details of genome maintenance, with potentially profound implications for human health.
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The Genetics of Nitrogen Use Efficiency in Crop Plants
Vol. 49 (2015), pp. 269–289More LessIn the past 50 years, the application of synthetic nitrogen (N) fertilizer to farmland resulted in a dramatic increase in crop yields but with considerable negative impacts on the environment. New solutions are therefore needed to simultaneously increase yields while maintaining, or preferably decreasing, applied N to maximize the nitrogen use efficiency (NUE) of crops. In this review, we outline the definition of NUE, the selection and development of NUE crops, and the factors that interact with NUE. In particular, we emphasize the challenges of developing crop plants with enhanced NUE, using more classical genetic approaches based on utilizing existing allelic variation for NUE traits. The challenges of phenotyping, mapping quantitative trait loci (QTLs), and selecting candidate genes for NUE improvement are described. In addition, we highlight the importance of different factors that lead to changes in the NUE components of nitrogen uptake efficiency (NUpE) and nitrogen utilization efficiency (NUtE).
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Eukaryotic Mismatch Repair in Relation to DNA Replication
Vol. 49 (2015), pp. 291–313More LessThree processes act in series to accurately replicate the eukaryotic nuclear genome. The major replicative DNA polymerases strongly prevent mismatch formation, occasional mismatches that do form are proofread during replication, and rare mismatches that escape proofreading are corrected by mismatch repair (MMR). This review focuses on MMR in light of increasing knowledge about nuclear DNA replication enzymology and the rate and specificity with which mismatches are generated during leading- and lagging-strand replication. We consider differences in MMR efficiency in relation to mismatch recognition, signaling to direct MMR to the nascent strand, mismatch removal, and the timing of MMR. These studies are refining our understanding of relationships between generating and repairing replication errors to achieve accurate replication of both DNA strands of the nuclear genome.
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Population Genomics for Understanding Adaptation in Wild Plant Species
Vol. 49 (2015), pp. 315–338More LessDarwin's theory of evolution by natural selection is the foundation of modern biology. However, it has proven remarkably difficult to demonstrate at the genetic, genomic, and population level exactly how wild species adapt to their natural environments. We discuss how one can use large sets of multiple genome sequences from wild populations to understand adaptation, with an emphasis on the small herbaceous plant Arabidopsis thaliana. We present motivation for such studies; summarize progress in describing whole-genome, species-wide sequence variation; and then discuss what insights have emerged from these resources, either based on sequence information alone or in combination with phenotypic data. We conclude with thoughts on opportunities with other plant species and the impact of expected progress in sequencing technology and genome engineering for studying adaptation in nature.
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Nonsense-Mediated mRNA Decay: Degradation of Defective Transcripts Is Only Part of the Story
Feng He, and Allan JacobsonVol. 49 (2015), pp. 339–366More LessNonsense-mediated mRNA decay (NMD) is a eukaryotic surveillance mechanism that monitors cytoplasmic mRNA translation and targets mRNAs undergoing premature translation termination for rapid degradation. From yeasts to humans, activation of NMD requires the function of the three conserved Upf factors: Upf1, Upf2, and Upf3. Here, we summarize the progress in our understanding of the molecular mechanisms of NMD in several model systems and discuss recent experiments that address the roles of Upf1, the principal regulator of NMD, in the initial targeting and final degradation of NMD-susceptible mRNAs. We propose a unified model for NMD in which the Upf factors provide several functions during premature termination, including the stimulation of release factor activity and the dissociation and recycling of ribosomal subunits. In this model, the ultimate degradation of the mRNA is the last step in a complex premature termination process.
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Accelerating Discovery and Functional Analysis of Small RNAs with New Technologies
Lars Barquist, and Jörg VogelVol. 49 (2015), pp. 367–394More LessOver the past decade, bacterial small RNAs (sRNAs) have gone from a biological curiosity to being recognized as a major class of regulatory molecules. High-throughput methods for sampling the transcriptional output of bacterial cells demonstrate that sRNAs are universal features of bacterial transcriptomes, are plentiful, and appear to vary extensively over evolutionary time. With ever more bacteria coming under study, the question becomes how can we accelerate the discovery and functional characterization of sRNAs in diverse organisms. New technologies built on high-throughput sequencing are emerging that can rapidly provide global insight into the numbers and functions of sRNAs in bacteria of interest, providing information that can shape hypotheses and guide research. In this review, we describe recent developments in transcriptomics (RNA-seq) and functional genomics that we expect to help us develop an integrated, systems-level view of sRNA biology in bacteria.
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Meiotic Silencing in Mammals
Vol. 49 (2015), pp. 395–412More LessMeiosis is essential for reproduction in sexually reproducing organisms. A key stage in meiosis is the synapsis of maternal and paternal homologous chromosomes, accompanied by exchange of genetic material to generate crossovers. A decade ago, studies found that when chromosomes fail to synapse, the many hundreds of genes housed within them are transcriptionally inactivated. This process, meiotic silencing, is conserved in all mammals studied to date, but its purpose is not yet defined. Here, I review the molecular genetics of meiotic silencing and consider the many potential functions that it could serve in the mammalian germ line. In addition, I discuss how meiotic silencing influences sex differences in meiotic infertility and the profound impact that meiotic silencing has had on the evolution of mammalian sex chromosomes.
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Neural Regulatory Pathways of Feeding and Fat in Caenorhabditis elegans
Vol. 49 (2015), pp. 413–438More LessThe compact nervous system of Caenorhabditis elegans and its genetic tractability are features that make this organism highly suitable for investigating energy balance in an animal system. Here, we focus on molecular components and organizational principles emerging from the investigation of pathways that largely originate in the nervous system and regulate feeding behavior but also peripheral fat regulation through neuroendocrine signaling. We provide an overview of studies aimed at understanding how C. elegans integrate internal and external cues in feeding behavior. We highlight some of the similarities and differences in energy balance between C. elegans and mammals. We also provide our perspective on unresolved issues, both conceptual and technical, that we believe have hampered critical evaluation of findings relevant to fat regulation in C. elegans.
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Accessing the Inaccessible: The Organization, Transcription, Replication, and Repair of Heterochromatin in Plants
Vol. 49 (2015), pp. 439–459More LessEukaryotic genomes often contain large quantities of potentially deleterious sequences, such as transposons. One strategy for mitigating this risk is to package such sequences into so-called constitutive heterochromatin, where the dense chromatin environment is thought to inhibit transcription by excluding transcription factors and RNA polymerase. This type of model makes it tempting to think of heterochromatin as an inert region that is isolated from the rest of the nucleus. Recent work on heterochromatin, however, reveals that it is a dynamic environment. Despite its dense packaging, heterochromatin must remain accessible for a host of processes, including DNA replication and repair, and, paradoxically, transcription. In plants, transcripts produced by specialized RNA polymerases are used to target regions of the genome for silencing via DNA methylation. Thus, the maintenance of heterochromatin requires a careful balancing act of access and exclusion, which is achieved through the action of a host of interrelated pathways.
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Genetic and Epigenetic Regulation of Human Cardiac Reprogramming and Differentiation in Regenerative Medicine
Vol. 49 (2015), pp. 461–484More LessRegeneration or replacement of lost cardiomyocytes within the heart has the potential to revolutionize cardiovascular medicine. Numerous methodologies have been used to achieve this aim, including the engraftment of bone marrow- and heart-derived cells as well as the identification of modulators of adult cardiomyocyte proliferation. Recently, the conversion of human somatic cells into induced pluripotent stem cells and induced cardiomyocyte-like cells has transformed potential approaches toward this goal, and the engraftment of cardiac progenitors derived from human embryonic stem cells into patients is now feasible. Here we review recent advances in our understanding of the genetic and epigenetic control of human cardiogenesis, cardiac differentiation, and the induced reprogramming of somatic cells to cardiomyocytes. We also cover genetic programs for inducing the proliferation of endogenous cardiomyocytes and discuss the genetic state of cells used in cardiac regenerative medicine.
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Giving Time Purpose: The Synechococcus elongatus Clock in a Broader Network Context
Vol. 49 (2015), pp. 485–505More LessEarly research on the cyanobacterial clock focused on characterizing the genes needed to keep, entrain, and convey time within the cell. As the scope of assays used in molecular genetics has expanded to capture systems-level properties (e.g., RNA-seq, ChIP-seq, metabolomics, high-throughput screening of genetic variants), so has our understanding of how the clock fits within and influences a broader cellular context. Here we review the work that has established a global perspective of the clock, with a focus on (a) an emerging network-centric view of clock architecture, (b) mechanistic insights into how temporal and environmental cues are transmitted and integrated within this network, (c) the systematic alteration of gene expression and cellular metabolism by the clock, and (d) insights into the evolution of temporal control in cyanobacteria.
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The Biology and Evolution of Mammalian Y Chromosomes
Vol. 49 (2015), pp. 507–527More LessMammals have the oldest sex chromosome system known: the mammalian X and Y chromosomes evolved from ordinary autosomes beginning at least 180 million years ago. Despite their shared ancestry, mammalian Y chromosomes display enormous variation among species in size, gene content, and structural complexity. Several unique features of the Y chromosome—its lack of a homologous partner for crossing over, its functional specialization for spermatogenesis, and its high degree of sequence amplification—contribute to this extreme variation. However, amid this evolutionary turmoil many commonalities have been revealed that have contributed to our understanding of the selective pressures driving the evolution and biology of the Y chromosome. Two biological themes have defined Y-chromosome research over the past six decades: testis determination and spermatogenesis. A third biological theme begins to emerge from recent insights into the Y chromosome's roles beyond the reproductive tract—a theme that promises to broaden the reach of Y-chromosome research by shedding light on fundamental sex differences in human health and disease.
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Conservation of Planar Polarity Pathway Function Across the Animal Kingdom
Vol. 49 (2015), pp. 529–551More LessPlanar polarity is a well-studied phenomenon resulting in the directional coordination of cells in the plane of a tissue. In invertebrates and vertebrates, planar polarity is established and maintained by the largely independent core and Fat/Dachsous/Four-jointed (Ft-Ds-Fj) pathways. Loss of function of these pathways can result in a wide range of developmental or cellular defects, including failure of gastrulation and problems with placement and function of cilia. This review discusses the conservation of these pathways across the animal kingdom. The lack of vital core pathway components in basal metazoans suggests that the core planar polarity pathway evolved shortly after, but not necessarily alongside, the emergence of multicellularity.
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Understanding Metabolic Regulation at a Systems Level: Metabolite Sensing, Mathematical Predictions, and Model Organisms
Vol. 49 (2015), pp. 553–575More LessMetabolic networks are extensively regulated to facilitate tissue-specific metabolic programs and robustly maintain homeostasis in response to dietary changes. Homeostatic metabolic regulation is achieved through metabolite sensing coupled to feedback regulation of metabolic enzyme activity or expression. With a wealth of transcriptomic, proteomic, and metabolomic data available for different cell types across various conditions, we are challenged with understanding global metabolic network regulation and the resulting metabolic outputs. Stoichiometric metabolic network modeling integrated with “omics” data has addressed this challenge by generating nonintuitive, testable hypotheses about metabolic flux rewiring. Model organism studies have also yielded novel insight into metabolic networks. This review covers three topics: the feedback loops inherent in metabolic regulatory networks, metabolic network modeling, and interspecies studies utilizing Caenorhabditis elegans and various bacterial diets that have revealed novel metabolic paradigms.
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Integrative and Conjugative Elements (ICEs): What They Do and How They Work
Vol. 49 (2015), pp. 577–601More LessHorizontal gene transfer plays a major role in microbial evolution, allowing microbes to acquire new genes and phenotypes. Integrative and conjugative elements (ICEs, a.k.a. conjugative transposons) are modular mobile genetic elements integrated into a host genome and are passively propagated during chromosomal replication and cell division. Induction of ICE gene expression leads to excision, production of the conserved conjugation machinery (a type IV secretion system), and the potential to transfer DNA to appropriate recipients. ICEs typically contain cargo genes that are not usually related to the ICE life cycle and that confer phenotypes to host cells. We summarize the life cycle and discovery of ICEs, some of the regulatory mechanisms, and how the types of cargo have influenced our view of ICEs. We discuss how ICEs can acquire new cargo genes and describe challenges to the field and various perspectives on ICE biology.
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General Stress Signaling in the Alphaproteobacteria
Vol. 49 (2015), pp. 603–625More LessThe Alphaproteobacteria uniquely integrate features of two-component signal transduction and alternative σ factor regulation to control transcription of genes that ensure growth and survival across a range of stress conditions. Research over the past decade has led to the discovery of the key molecular players of this general stress response (GSR) system, including the sigma factor σEcfG, its anti-σ factor NepR, and the anti-anti-σ factor PhyR. The central molecular event of GSR activation entails aspartyl phosphorylation of PhyR, which promotes its binding to NepR and thereby releases σEcfG to associate with RNAP and direct transcription. Recent studies are providing a new understanding of complex, multilayered sensory networks that activate and repress this central protein partner switch. This review synthesizes our structural and functional understanding of the core GSR regulatory proteins and highlights emerging data that are defining the systems that regulate GSR transcription in a variety of species.
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Gene Positioning Effects on Expression in Eukaryotes
Vol. 49 (2015), pp. 627–646More LessThe packaging and organization of the genome within the eukaryotic interphase nucleus directly influence how the genes are expressed. An underappreciated aspect of genome structure is that it is highly dynamic and that the physical positioning of a gene can impart control over its transcriptional status. In this review, we assess the current knowledge of how gene positioning at different levels of genome organization can directly influence gene expression during interphase. The levels of organization discussed include chromatin looping, topologically associated domains, chromosome territories, and nuclear compartments. We discuss specific studies demonstrating that gene positioning is a dynamic and highly regulated feature of the eukaryotic genome that allows for the essential spatiotemporal regulation of genes.
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Asymmetry of the Brain: Development and Implications
Vol. 49 (2015), pp. 647–672More LessAlthough the left and right hemispheres of our brains develop with a high degree of symmetry at both the anatomical and functional levels, it has become clear that subtle structural differences exist between the two sides and that each is dominant in processing specific cognitive tasks. As the result of evolutionary conservation or convergence, lateralization of the brain is found in both vertebrates and invertebrates, suggesting that it provides significant fitness for animal life. This widespread feature of hemispheric specialization has allowed the emergence of model systems to study its development and, in some cases, to link anatomical asymmetries to brain function and behavior. Here, we present some of what is known about brain asymmetry in humans and model organisms as well as what is known about the impact of environmental and genetic factors on brain asymmetry development. We specifically highlight the progress made in understanding the development of epithalamic asymmetries in zebrafish and how this model provides an exciting opportunity to address brain asymmetry at different levels of complexity.
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Modulation of Chromatin by Noncoding RNA
Vol. 49 (2015), pp. 673–695More LessNoncoding RNAs (ncRNAs) are remarkably powerful, flexible, and pervasive cellular regulators. The involvement of these molecules in virtually all aspects of eukaryotic chromatin function is notable. Long and short ncRNAs play broadly complementary roles in these processes. Short ncRNAs underlie a programmable system of chromatin modification that silences mobile elements, identifies boundaries, and initiates the formation of constitutive heterochromatin in yeast. In contrast, long noncoding RNAs (lncRNAs) enforce developmentally appropriate expression and switch gene expression programs. lncRNAs accomplish this through diverse mechanisms, but often by modulating the activity or localization of chromatin regulatory complexes. Both long and short ncRNAs play key roles in organization of complex genomes of higher eukaryotes, and their coordinated actions appear to underlie some of the more dramatic examples of epigenetic regulation. This review contrasts well-studied examples of chromatin regulation by RNA and introduces examples of coordination between these systems.
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Cell Competition During Growth and Regeneration
Vol. 49 (2015), pp. 697–718More LessTissue growth and regeneration are autonomous, stem-cell-mediated processes in which stem cells within the organ self-renew and differentiate to create new cells, leading to new tissue. The processes of growth and regeneration require communication and interplay between neighboring cells. In particular, cell competition, which is a process in which viable cells are actively eliminated by more competitive cells, has been increasingly implicated to play an important role. Here, we discuss the existing literature regarding the current landscape of cell competition, including classical pathways and models, fitness fingerprint mechanisms, and immune system mechanisms of cell competition. We further discuss the clinical relevance of cell competition in the physiological processes of tissue growth and regeneration, highlighting studies in clinically important disease models, including oncological, neurological, and cardiovascular diseases.
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Previous Volumes
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Volume 57 (2023)
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Volume 56 (2022)
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Volume 55 (2021)
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Volume 54 (2020)
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Volume 53 (2019)
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Volume 52 (2018)
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Volume 51 (2017)
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Volume 50 (2016)
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Volume 49 (2015)
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Volume 48 (2014)
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Volume 47 (2013)
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Volume 46 (2012)
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Volume 45 (2011)
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Volume 44 (2010)
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Volume 43 (2009)
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Volume 42 (2008)
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Volume 41 (2007)
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Volume 40 (2006)
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Volume 39 (2005)
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Volume 38 (2004)
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Volume 37 (2003)
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Volume 36 (2002)
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Volume 35 (2001)
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Volume 34 (2000)
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Volume 33 (1999)
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Volume 32 (1998)
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Volume 31 (1997)
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Volume 30 (1996)
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Volume 29 (1995)
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Volume 28 (1994)
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Volume 27 (1993)
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Volume 26 (1992)
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Volume 25 (1991)
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Volume 24 (1990)
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Volume 23 (1989)
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Volume 22 (1988)
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Volume 21 (1987)
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Volume 20 (1986)
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Volume 19 (1985)
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Volume 18 (1984)
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Volume 17 (1983)
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Volume 16 (1982)
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Volume 15 (1981)
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Volume 14 (1980)
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Volume 13 (1979)
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Volume 12 (1978)
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Volume 11 (1977)
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Volume 10 (1976)
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Volume 9 (1975)
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Volume 8 (1974)
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Volume 7 (1973)
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Volume 6 (1972)
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Volume 5 (1971)
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Volume 4 (1970)
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Volume 3 (1969)
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Volume 2 (1968)
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Volume 1 (1967)
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Volume 0 (1932)