Actors with Multiple Roles: Pleiotropic Enhancers and the Paradigm of Enhancer Modularity.
kel N Abstract The current paradigm in the field of gene regulation postulates that regulatory information for generating gene expression is organized into modules (enhancers), each containing the information for driving gene expression in a single spatiotemporal context. This modular organization is thought to facilitate the evolution of gene expression by minimizing pleiotropic effects. Here we review recent studies that provide evidence of quite the opposite: (i) enhancers can function in multiple developmental contexts, implying that enhancers can be pleiotropic, (ii) transcription factor binding sites within ...
Source: Trends in Genetics : TIG - April 17, 2019 Category: Genetics & Stem Cells Authors: Sabarís G, Laiker I, Preger-Ben Noon E, Frankel N Tags: Trends Genet Source Type: research

Models and Nomenclature for Cytoplasmic Incompatibility: Caution over Premature Conclusions - A Response to Beckmann et al.
Conclusions - A Response to Beckmann et al. Trends Genet. 2019 Apr 16;: Authors: Shropshire JD, Leigh B, Bordenstein SR, Duplouy A, Riegler M, Brownlie JC, Bordenstein SR PMID: 31003827 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - April 16, 2019 Category: Genetics & Stem Cells Authors: Shropshire JD, Leigh B, Bordenstein SR, Duplouy A, Riegler M, Brownlie JC, Bordenstein SR Tags: Trends Genet Source Type: research

Caution Does Not Preclude Predictive and Testable Models of Cytoplasmic Incompatibility: A Reply to Shropshire et al.
lat S PMID: 30979535 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - April 9, 2019 Category: Genetics & Stem Cells Authors: Beckmann JF, Bonneau M, Chen H, Hochstrasser M, Poinsot D, Merçot H, Weill M, Sicard M, Charlat S Tags: Trends Genet Source Type: research

Tools To Live By: Bacterial DNA Structures Illuminate Cancer.
Abstract Holliday junctions (HJs) are DNA intermediates in homology-directed DNA repair and replication stalling, but until recently were undetectable in living cells. We review how an engineered protein that traps and labels HJs in Escherichia coli illuminates the biology of DNA and cancer. HJ chromatin immunoprecipitation with deep sequencing (ChIP-seq) analysis showed the directionality of double-strand break (DSB) repair in the E. coli genome. Quantification of HJs as fluorescent foci in live cells revealed that the commonest spontaneous problem repaired via HJs is replication-dependent single-stranded DNA gap...
Source: Trends in Genetics : TIG - April 5, 2019 Category: Genetics & Stem Cells Authors: Xia J, Mei Q, Rosenberg SM Tags: Trends Genet Source Type: research

The Promise of Paleogenomics Beyond Our Own Species.
Abstract Paleogenomics, also known as genome-wide ancient DNA analysis, is transforming our understanding of the human past, but has been much less intensively used to understand the history of other species. However, paleogenomic studies of non-human animals and plants have the potential to address an equally rich range of evolutionary, paleoecological, paleoenvironmental, and archaeological research questions. Three recent case studies of cave bears, horses, and maize provide examples of the ways that paleogenomics can be used to examine potential causes of extinctions and dynamic processes of domestication. Muc...
Source: Trends in Genetics : TIG - April 3, 2019 Category: Genetics & Stem Cells Authors: Brunson K, Reich D Tags: Trends Genet Source Type: research

Diversity and Determinants of Meiotic Recombination Landscapes.
Abstract Despite the universal importance of meiotic recombination for generating genetic diversity, numbers and distribution of recombination events along chromosomes vary among species, genotypes within species, and between sexes. Some interspecies differences stem from the diversity of genome size and composition among eukaryotes. Large-genome species, such as humans and most crops, display recombination landscapes that are different from those of small-genome yeasts. Chromatin patterns, including histone modifications and DNA methylation, are also responsible for interspecies differences as well as differences...
Source: Trends in Genetics : TIG - April 1, 2019 Category: Genetics & Stem Cells Authors: Zelkowski M, Olson MA, Wang M, Pawlowski WP Tags: Trends Genet Source Type: research

Progress in Polygenic Composite Scores in Alzheimer's and Other Complex Diseases.
Abstract Advances in high-throughput genotyping and next-generation sequencing (NGS) coupled with larger sample sizes brings the realization of precision medicine closer than ever. Polygenic approaches incorporating the aggregate influence of multiple genetic variants can contribute to a better understanding of the genetic architecture of many complex diseases and facilitate patient stratification. This review addresses polygenic concepts, methodological developments, hypotheses, and key issues in study design. Polygenic risk scores (PRSs) have been applied to many complex diseases and here we focus on Alzheimer's...
Source: Trends in Genetics : TIG - March 25, 2019 Category: Genetics & Stem Cells Authors: Chasioti D, Yan J, Nho K, Saykin AJ Tags: Trends Genet Source Type: research

Genetic Control of Gonadal Sex Determination and Development.
Nef S Abstract Sex determination is the process by which the bipotential gonads develop as either testes or ovaries. With two distinct potential outcomes, the gonadal primordium offers a unique model for the study of cell fate specification and how distinct cell populations diverge from multipotent progenitors. This review focuses on recent advances in our understanding of the genetic programs and epigenetic mechanisms that regulate gonadal sex determination and the regulation of cell fate commitment in the bipotential gonads. We rely primarily on mouse data to illuminate the complex and dynamic genetic programs c...
Source: Trends in Genetics : TIG - March 19, 2019 Category: Genetics & Stem Cells Authors: Stévant I, Nef S Tags: Trends Genet Source Type: research

A Snapshot on the Cis Chromatin Response to DNA Double-Strand Breaks.
Abstract In eukaryotes, detection and repair of DNA double-strand breaks (DSBs) operate within chromatin, an incredibly complex structure that tightly packages and regulates DNA metabolism. Chromatin participates in the repair of these lesions at multiple steps, from detection to genomic sequence recovery and chromatin is itself extensively modified during the repair process. In recent years, new methodologies and dedicated techniques have expanded the experimental toolbox, opening up a new era granting the high-resolution analysis of chromatin modifications at annotated DSBs in a genome-wide manner. A complex pic...
Source: Trends in Genetics : TIG - March 18, 2019 Category: Genetics & Stem Cells Authors: Clouaire T, Legube G Tags: Trends Genet Source Type: research

Candida albicans: An Emerging Yeast Model to Study Eukaryotic Genome Plasticity.
Abstract Saccharomyces cerevisiae and Schizosaccharomyces pombe have served as uncontested unicellular model organisms, as major discoveries made in the field of genome biology using yeast genetics have proved to be relevant from yeast to humans. The yeast Candida albicans has attracted much attention because of its ability to switch between a harmless commensal and a dreaded human pathogen. C. albicans bears unique features regarding its life cycle, genome structure, and dynamics, and their links to cell biology and adaptation to environmental challenges. Examples include a unique reproduction cycle with haploid,...
Source: Trends in Genetics : TIG - February 27, 2019 Category: Genetics & Stem Cells Authors: Legrand M, Jaitly P, Feri A, d'Enfert C, Sanyal K Tags: Trends Genet Source Type: research

Making a Murderer: The Evolutionary Framing of Hybrid Gamete-Killers.
Abstract Recent molecular investigations of hybrid incompatibilities have revealed fascinating patterns of genetic interactions that have been interpreted as the remnants of a history of selfish evolution. Instead of framing hybrid incompatibilities in light of genetic conflict, we advocate assuming their innocence. Researchers must build a strong theory for each case, supported by population genetic evidence, such that the role of conflict in the evolution of a hybrid incompatibility can be proven beyond reasonable doubt. This will require careful investigation of the evolutionary history of these incompatibiliti...
Source: Trends in Genetics : TIG - February 27, 2019 Category: Genetics & Stem Cells Authors: Sweigart AL, Brandvain Y, Fishman L Tags: Trends Genet Source Type: research

Magic Traits in Magic Fish: Understanding Color Pattern Evolution Using Reef Fish.
cute;rich B Abstract Color patterns provide easy access to phenotypic diversity and allow the questioning of the adaptive value of traits or the constraints acting on phenotypic evolution. Reef fish offer a unique opportunity to address such questions because they are ecologically and phylogenetically diverse and have the largest variety of pigment cell types known in vertebrates. In addition to recent development of their genetic resources, reef fish also constitute experimental models that allow the discrimination of ecological, developmental, and evolutionary processes at work. Here, we emphasize how the study ...
Source: Trends in Genetics : TIG - February 25, 2019 Category: Genetics & Stem Cells Authors: Salis P, Lorin T, Laudet V, Frédérich B Tags: Trends Genet Source Type: research

Diverse Genome Topologies Characterize Dosage Compensation across Species.
Abstract Dosage compensation is the process by which transcript levels of the X chromosome are equalized with those of autosomes. Although diverse mechanisms of dosage compensation have evolved across species, these mechanisms all involve distinguishing the X chromosome from autosomes. Because one chromosome is singled out from other chromosomes for precise regulation, dosage compensation serves as an important model for understanding how specific cis-elements are identified within the highly compacted 3D genome to co-regulate thousands of genes. Recently, multiple genomic approaches have provided key insights int...
Source: Trends in Genetics : TIG - February 23, 2019 Category: Genetics & Stem Cells Authors: Jordan W, Rieder LE, Larschan E Tags: Trends Genet Source Type: research

Substitutions Are Boring: Some Arguments about Parallel Mutations and High Mutation Rates.
Abstract Extant genomes are largely shaped by global transposition, copy-number fluctuation, and rearrangement of DNA sequences rather than by substitutions of single nucleotides. Although many of these large-scale mutations have low probabilities and are unlikely to repeat, others are recurrent or predictable in their effects, leading to stereotyped genome architectures and genetic variation in both eukaryotes and prokaryotes. Such recurrent, parallel mutation modes can profoundly shape the paths taken by evolution and undermine common models of evolutionary genetics. Similar patterns are also evident at the smal...
Source: Trends in Genetics : TIG - February 20, 2019 Category: Genetics & Stem Cells Authors: Press MO, Hall AN, Morton EA, Queitsch C Tags: Trends Genet Source Type: research

Electronic Health Records Are the Next Frontier for the Genetics of Substance Use Disorders.
Abstract Compared with other psychiatric disorders of similar heritabilities, the progress of substance use disorders (SUD) genetics has been slow. With the growing availability of large-scale biobanks with extensive phenotypes from electronic health records (EHR) and genotypes across millions of individuals, this platform is the next tool to accelerate SUD genetics research. PMID: 30797598 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - February 20, 2019 Category: Genetics & Stem Cells Authors: Sanchez-Roige S, Palmer AA Tags: Trends Genet Source Type: research

Consequences of Genomic Diversification Induced by Segregation Errors.
Abstract Chromosome segregation errors are an important source of genomic diversification that promote tumor heterogeneity and evolution. However, the aneuploidy induced by chromosome missegregations causes cellular stress at many levels, raising the question of how segregation errors can be tolerated in cancer. Additionally, we now know that chromosome segregation errors can lead to activation of the innate immune system, producing yet another challenge for chromosomally unstable cells. These observations imply that several liabilities are encountered during tumor evolution, which could potentially be exploited f...
Source: Trends in Genetics : TIG - February 8, 2019 Category: Genetics & Stem Cells Authors: Soto M, Raaijmakers JA, Medema RH Tags: Trends Genet Source Type: research

Data Lakes, Clouds, and Commons: A Review of Platforms for Analyzing and Sharing Genomic Data.
Abstract Data commons collate data with cloud computing infrastructure and commonly used software services, tools, and applications to create biomedical resources for the large-scale management, analysis, harmonization, and sharing of biomedical data. Over the past few years, data commons have been used to analyze, harmonize, and share large-scale genomics datasets. Data ecosystems can be built by interoperating multiple data commons. It can be quite labor intensive to curate, import, and analyze the data in a data commons. Data lakes provide an alternative to data commons and simply provide access to data, with t...
Source: Trends in Genetics : TIG - January 25, 2019 Category: Genetics & Stem Cells Authors: Grossman RL Tags: Trends Genet Source Type: research

Mechanisms of Mitochondrial DNA Deletion Formation.
Abstract Mitochondrial DNA (mtDNA) encodes a subset of genes which are essential for oxidative phosphorylation. Deletions in the mtDNA can ablate a number of these genes and result in mitochondrial dysfunction, which is associated with bona fide mitochondrial disorders. Although mtDNA deletions are thought to occur as a result of replication errors or following double-strand breaks, the exact mechanism(s) behind deletion formation have yet to be determined. In this review we discuss the current knowledge about the fate of mtDNA following double-strand breaks, including the molecular players which mediate the degra...
Source: Trends in Genetics : TIG - January 25, 2019 Category: Genetics & Stem Cells Authors: Nissanka N, Minczuk M, Moraes CT Tags: Trends Genet Source Type: research

The Toxin-Antidote Model of Cytoplasmic Incompatibility: Genetics and Evolutionary Implications.
lat S Abstract Wolbachia bacteria inhabit the cells of about half of all arthropod species, an unparalleled success stemming in large part from selfish invasive strategies. Cytoplasmic incompatibility (CI), whereby the symbiont makes itself essential to embryo viability, is the most common of these and constitutes a promising weapon against vector-borne diseases. After decades of theoretical and experimental struggle, major recent advances have been made toward a molecular understanding of this phenomenon. As pieces of the puzzle come together, from yeast and Drosophila fly transgenesis to CI diversity patterns in...
Source: Trends in Genetics : TIG - January 23, 2019 Category: Genetics & Stem Cells Authors: Beckmann JF, Bonneau M, Chen H, Hochstrasser M, Poinsot D, Merçot H, Weill M, Sicard M, Charlat S Tags: Trends Genet Source Type: research

The Fanconi Anemia Pathway and Fertility.
Abstract Fanconi anemia (FA) is a life-threatening syndrome characterized by bone marrow failure and cancer predispositions. The past two decades have seen an explosion of data in the FA field, both in humans and other organisms, following the cloning of 22 FA genes. A common but notably understudied clinical feature of the disease is the reduced fertility of individuals with FA. This review focuses on the known causes of reduced fertility in FA, and integrates them with the emerging role of the FA pathway in double-strand break (DSB) repair at meiosis in a variety of organisms, as well as providing future directi...
Source: Trends in Genetics : TIG - January 22, 2019 Category: Genetics & Stem Cells Authors: Tsui V, Crismani W Tags: Trends Genet Source Type: research

miRNA Targeting: Growing beyond the Seed.
Abstract miRNAs are small RNAs that guide Argonaute proteins to specific target mRNAs to repress their translation and stability. Canonically, miRNA targeting is reliant on base pairing of the seed region, nucleotides 2-7, of the miRNA to sites in mRNA 3' untranslated regions. Recently, the 3' half of the miRNA has gained attention for newly appreciated roles in regulating target specificity and regulation. In addition, the extent of pairing to the miRNA 3' end can influence the stability of the miRNA itself. These findings highlight the importance of sequences beyond the seed in controlling the function and exist...
Source: Trends in Genetics : TIG - January 9, 2019 Category: Genetics & Stem Cells Authors: Chipman LB, Pasquinelli AE Tags: Trends Genet Source Type: research

Translation of Small Open Reading Frames: Roles in Regulation and Evolutionary Innovation.
e; MM Abstract The translatome can be defined as the sum of the RNA sequences that are translated into proteins in the cell by the ribosomal machinery. Until recently, it was generally assumed that the translatome was essentially restricted to evolutionary conserved proteins encoded by the set of annotated protein-coding genes. However, it has become increasingly clear that it also includes small regulatory open reading frames (ORFs), functional micropeptides, de novo proteins, and the pervasive translation of likely nonfunctional proteins. Many of these ORFs have been discovered thanks to the development of ribos...
Source: Trends in Genetics : TIG - December 31, 2018 Category: Genetics & Stem Cells Authors: Ruiz-Orera J, Albà MM Tags: Trends Genet Source Type: research

Multiple Roles for Mono- and Poly(ADP-Ribose) in Regulating Stress Responses.
Abstract Although stress-induced synthesis of mono(ADP-ribose) (mADPr) and poly(ADP-ribose) (pADPr) conjugates by pADPr polymerase (PARP) enzymes has been studied extensively, the removal and degradation of pADPr, as well as the fate of ADPr metabolites, have received less attention. The observations that stress-induced pADPr undergoes rapid turnover, and that deficiencies in ADPr degradation phenocopy loss of pADPr synthesis, suggest that ADPr degradation is fundamentally important to the cellular stress response. Recent work has identified several distinct families of pADPr hydrolases that can degrade pADPr to r...
Source: Trends in Genetics : TIG - December 27, 2018 Category: Genetics & Stem Cells Authors: Qi H, Price BD, Day TA Tags: Trends Genet Source Type: research

Support for Living Stock Collections: A Mammalian Stock Center Perspective.
Abstract The living stock collections represent an indispensable resource for life scientists. Their uninterrupted operation should combine high quality standards, cost-effectiveness, wide accessibility, and sustainability. Mammalian stock collections, especially those involving diversified animals, face some unique challenges that may disrupt their smooth operation if not addressed. PMID: 30587379 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - December 23, 2018 Category: Genetics & Stem Cells Authors: Kiaris H Tags: Trends Genet Source Type: research

Chromatin Interactions and Regulatory Elements in Cancer: From Bench to Bedside.
Abstract Chromatin interactions regulate gene expression by bringing distal regulatory elements, such as super-enhancers, to promoters in close spatial proximity. It has been recognized that in cancer, chromatin interactions can be dysregulated, leading to aberrant oncogene expression. Chromatin interactions may potentially serve as biomarkers, or be modulated via CRISPR therapy and small molecule inhibitors against transcription. However, these methods face challenges that must be resolved and raise questions for further research. Understanding chromatin interactions is essential for safety aspects of anticancer ...
Source: Trends in Genetics : TIG - December 18, 2018 Category: Genetics & Stem Cells Authors: See YX, Wang BZ, Fullwood MJ Tags: Trends Genet Source Type: research

Small Nucleolar RNAs Tell a Different Tale.
Abstract Transcribing RNA Polymerase II interacts with multiple factors that orchestrate maturation and stabilisation of messenger RNA. For the majority of noncoding RNAs, the polymerase complex employs entirely different strategies, which usually direct the nascent transcript to ribonucleolytic degradation. However, some noncoding RNA classes use endo- and exonucleases to achieve functionality. Here we review processing of small nucleolar RNAs that are transcribed by RNA Polymerase II as precursors, and whose 5' and 3' ends undergo processing to release mature, functional molecules. The maturation strategies of t...
Source: Trends in Genetics : TIG - December 15, 2018 Category: Genetics & Stem Cells Authors: Kufel J, Grzechnik P Tags: Trends Genet Source Type: research

Studying Transcriptional Enhancers: The Founder Fallacy, Validation Creep, and Other Biases.
Abstract Transcriptional enhancers play a major role in regulating metazoan gene expression. Recent developments in genomics and next-generation sequencing have accelerated and revitalized the study of this important class of sequence elements. Increased interest and attention, however, has also led to troubling trends in the enhancer literature. In this Opinion, I describe some of these issues and show how they arise from shifting and nonuniform enhancer definitions, and genome-era biases. I discuss how they can lead to interpretative errors and an unduly narrow focus on certain aspects of enhancer biology to the...
Source: Trends in Genetics : TIG - December 12, 2018 Category: Genetics & Stem Cells Authors: Halfon MS Tags: Trends Genet Source Type: research

The Generic Facet of Hox Protein Function: (Trends in Genetics 34, 941-953, 2018).
PMID: 30529028 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - December 7, 2018 Category: Genetics & Stem Cells Authors: Saurin AJ, Delfini MC, Maurel-Zaffran C, Graba Y Tags: Trends Genet Source Type: research

Non-duplex G-Quadruplex Structures Emerge as Mediators of Epigenetic Modifications.
Abstract The role of non-duplex DNA, the guanine-quadruplex structure in particular, is becoming widely appreciated. Increasing evidence in the last decade implicates quadruplexes in important processes such as transcription and replication. Interestingly, more recent work suggests roles for quadruplexes, in association with quadruplex-interacting proteins, in epigenetics through both DNA and histone modifications. Here, we review the effect of the quadruplex structure on post-replication epigenetic memory and quadruplex-induced promoter DNA/histone modifications. Furthermore, we highlight the epigenetic state of ...
Source: Trends in Genetics : TIG - December 4, 2018 Category: Genetics & Stem Cells Authors: Mukherjee AK, Sharma S, Chowdhury S Tags: Trends Genet Source Type: research

Improving Estimates of Compensatory cis-trans Regulatory Divergence.
PMID: 30509787 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - November 30, 2018 Category: Genetics & Stem Cells Authors: Fraser HB Tags: Trends Genet Source Type: research

Understanding Grass Domestication through Maize Mutants.
Abstract As an economically important model crop plant, rich in genetic resources, maize has been useful for uncovering the genetic pathways responsible for domestication and plant improvement. However, several of the pathways that have been shown by recent studies to be important for domestication and/or yield in other grasses function differently in maize. In several cases, this unexpectedly wide functional divergence between genes from closely related grasses appears to be due to alternative modes of regulation rather than to simple differences in protein function. This indicates that domestication genes need t...
Source: Trends in Genetics : TIG - November 30, 2018 Category: Genetics & Stem Cells Authors: Dong Z, Alexander M, Chuck G Tags: Trends Genet Source Type: research

Post-Translational Modification, Phase Separation, and Robust Gene Transcription.
Abstract A few recent reports reveal fundamental new insights into the intricate regulatory mechanisms that govern RNA polymerase II (Pol II)-mediated gene transcription. Whereas a histidine-rich domain (HRD) triggers phase separation, promoting transcription elongation, a phosphatase switch promotes transcription termination. A paradigm that might govern the underlying mechanisms leading to robust gene transcription is now starting to emerge. PMID: 30477958 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - November 23, 2018 Category: Genetics & Stem Cells Authors: Singh HR, Ostwal YB Tags: Trends Genet Source Type: research

Dissecting the Genetics of Osteoporosis using Systems Approaches.
Abstract Osteoporosis is a condition characterized by low bone mineral density (BMD) and an increased risk of fracture. Traits contributing to osteoporotic fracture are highly heritable, indicating that a comprehensive understanding of bone requires a thorough understanding of the genetic basis of bone traits. Towards this goal, genome-wide association studies (GWASs) have identified over 500 loci associated with bone traits. However, few of the responsible genes have been identified, and little is known of how these genes work together to influence systems-level bone function. In this review, we describe how syst...
Source: Trends in Genetics : TIG - November 20, 2018 Category: Genetics & Stem Cells Authors: Al-Barghouthi BM, Farber CR Tags: Trends Genet Source Type: research

Solving the Polyploid Mystery in Health and Disease.
Abstract Polyploidy (the more than doubling of a cell's genome) frequently arises during organogenesis, tissue repair, and age-associated diseases. Despite its prevalence, major gaps exist in how polyploid cells emerge and affect tissue function. Studies have begun to elucidate the signals required for polyploid cell growth as well as the advantages and disadvantages of polyploidy in health and disease. This review highlights the recent advances on the role and regulation of polyploidy in Drosophila and vertebrate models. The newly discovered versatility of polyploid cells has the potential to provide alternative ...
Source: Trends in Genetics : TIG - November 20, 2018 Category: Genetics & Stem Cells Authors: Gjelsvik KJ, Besen-McNally R, Losick VP Tags: Trends Genet Source Type: research

RNA Splicing and Disease: Animal Models to Therapies.
Abstract Alternative splicing of pre-mRNA increases genetic diversity, and recent studies estimate that most human multiexon genes are alternatively spliced. If this process is not highly regulated and accurate, it leads to mis-splicing events, which may result in proteins with altered function. A growing body of work has implicated mis-splicing events in a range of diseases, including cancer, neurodegenerative diseases, and muscular dystrophies. Understanding the mechanisms that cause aberrant splicing events and how this leads to disease is vital for designing effective therapeutic strategies. In this review, we...
Source: Trends in Genetics : TIG - November 19, 2018 Category: Genetics & Stem Cells Authors: Montes M, Sanford BL, Comiskey DF, Chandler DS Tags: Trends Genet Source Type: research

Knocking Out Enhancers to Enhance Epigenetic Research.
PMID: 30466730 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - November 3, 2018 Category: Genetics & Stem Cells Authors: Duester G Tags: Trends Genet Source Type: research

Whole-Genome Duplication and Yeast's Fruitful Way of Life.
lez A Abstract Studies on the fate of Saccharomyces cerevisiae paralogous gene pairs that arose through a whole-genome duplication event have shown diversification of retained duplicated genes. Paralogous functional specialization often results in improved function and/or novel function that could contribute to the adaptation of the organism to a new lifestyle. Here, we analyze and discuss particular case studies of paralogous functional diversification that could have played a role in the acquisition of yeast fermentative metabolism. PMID: 30366621 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - October 23, 2018 Category: Genetics & Stem Cells Authors: Escalera-Fanjul X, Quezada H, Riego-Ruiz L, González A Tags: Trends Genet Source Type: research

Genomic and Phenomic Research in the 21st Century.
Abstract The field of human genomics has changed dramatically over time. Initial genomic studies were predominantly restricted to rare disorders in small families. Over the past decade, researchers changed course from family-based studies and instead focused on common diseases and traits in populations of unrelated individuals. With further advancements in biobanking, computer science, electronic health record (EHR) data, and more affordable high-throughput genomics, we are experiencing a new paradigm in human genomic research. Rapidly changing technologies and resources now make it possible to study thousands of ...
Source: Trends in Genetics : TIG - October 17, 2018 Category: Genetics & Stem Cells Authors: Hebbring S Tags: Trends Genet Source Type: research

Post-transcriptional Regulatory Functions of Mammalian Pumilio Proteins.
Abstract Mammalian Pumilio proteins, PUM1 and PUM2, are members of the PUF family of sequence-specific RNA-binding proteins. In this review, we explore their mechanisms, regulatory networks, biological functions, and relevance to diseases. Pumilio proteins bind an extensive network of mRNAs and repress protein expression by inhibiting translation and promoting mRNA decay. Opposingly, in certain contexts, they can activate protein expression. Pumilio proteins also regulate noncoding (nc)RNAs. The ncRNA, ncRNA activated by DNA damage (NORAD), can in turn modulate Pumilio activity. Genetic analysis provides new insig...
Source: Trends in Genetics : TIG - October 10, 2018 Category: Genetics & Stem Cells Authors: Goldstrohm AC, Hall TMT, McKenney KM Tags: Trends Genet Source Type: research

Rhythms of the Genome: Circadian Dynamics from Chromatin Topology, Tissue-Specific Gene Expression, to Behavior.
Abstract Circadian rhythms in physiology and behavior evolved to resonate with daily cycles in the external environment. In mammals, organs orchestrate temporal physiology over the 24-h day, which requires extensive gene expression rhythms targeted to the right tissue. Although a core set of gene products oscillates across virtually all cell types, gene expression profiling across tissues over the 24-h day showed that rhythmic gene expression programs are tissue specific. We highlight recent progress in uncovering how the circadian clock interweaves with tissue-specific gene regulatory networks involving functions...
Source: Trends in Genetics : TIG - October 8, 2018 Category: Genetics & Stem Cells Authors: Yeung J, Naef F Tags: Trends Genet Source Type: research

The Birth of the 3D Genome during Early Embryonic Development.
Abstract The 3D structure of chromatin in the nucleus is important for the regulation of gene expression and the correct deployment of developmental programs. The differentiation of germ cells and early embryonic development (when the zygotic genome is activated and transcription is taking place for the first time) are accompanied by dramatic changes in gene expression and the epigenetic landscape. Recent studies used Hi-C to investigate the 3D chromatin organization during these developmental transitions, uncovering remarkable remodeling of the 3D genome. Here, we highlight the changes described so far and discus...
Source: Trends in Genetics : TIG - October 3, 2018 Category: Genetics & Stem Cells Authors: Hug CB, Vaquerizas JM Tags: Trends Genet Source Type: research

Wake-up Sleepy Gene: Reactivating Fetal Globin for β-Hemoglobinopathies.
Wake-up Sleepy Gene: Reactivating Fetal Globin for β-Hemoglobinopathies. Trends Genet. 2018 Oct 01;: Authors: Wienert B, Martyn GE, Funnell APW, Quinlan KGR, Crossley M Abstract Disorders in hemoglobin (hemoglobinopathies) were the first monogenic diseases to be characterized and remain among the most common and best understood genetic conditions. Moreover, the study of the β-globin locus provides a textbook example of developmental gene regulation. The fetal γ-globin genes (HBG1/HBG2) are ordinarily silenced around birth, whereupon their expression is replaced by the adult β-glob...
Source: Trends in Genetics : TIG - October 1, 2018 Category: Genetics & Stem Cells Authors: Wienert B, Martyn GE, Funnell APW, Quinlan KGR, Crossley M Tags: Trends Genet Source Type: research

Improving Estimates of Compensatory cis-trans Regulatory Divergence.
Abstract Interspecific hybrids have played a key role in research on gene expression regulation. A growing number of studies have measured genome-wide allele-specific expression in hybrids and observed that cis-regulatory changes often oppose trans-acting changes affecting the same genes, suggesting stabilizing selection for compensatory changes. However, the most common method for estimating these effects is biased, producing artifactual patterns of compensatory evolution. Here I introduce a simple modification leveraging biological replicates that ameliorates the bias. PMID: 30270122 [PubMed - as supplied b...
Source: Trends in Genetics : TIG - September 27, 2018 Category: Genetics & Stem Cells Authors: Fraser HB Tags: Trends Genet Source Type: research

Easy Access to and Applications of the Sequences of All Protein-Coding Genes of All Sequenced Mouse Strains.
Abstract An easily accessible and searchable overview of all protein sequences in the 36 genome-sequenced mouse strains, compared to those in the reference strain C57BL/6J, is now available, as well as an overview of the aberrant proteins in this reference strain. We provide an insight into the advantages of using these databases. PMID: 30243593 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - September 19, 2018 Category: Genetics & Stem Cells Authors: Timmermans S, Libert C Tags: Trends Genet Source Type: research

The Generic Facet of Hox Protein Function.
Abstract Hox transcription factors are essential to promote morphological diversification of the animal body. A substantial number of studies have focused on how Hox proteins reach functional specificity, an issue that arises from the fact that these transcription factors control distinct developmental functions despite sharing similar molecular properties. In this review, we highlight that, besides specific functions, for which these transcription factors are renowned, Hox proteins also often have nonspecific functions. We next discuss some emerging principles of these generic functions and how they relate to spe...
Source: Trends in Genetics : TIG - September 18, 2018 Category: Genetics & Stem Cells Authors: Saurin AJ, Delfini MC, Maurel-Zaffran C, Graba Y Tags: Trends Genet Source Type: research

Drilling for Insight: Forecasting Phenotype from Genotype.
Abstract The manifestation of disease can vary substantially from person to person. Yet, much of the emphasis of genomics in individualized medicine has been on linking genetic variants to broad disease categories. A new approach takes a first step towards predicting detailed phenotypic information from disease-causative variants. PMID: 30220472 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - September 13, 2018 Category: Genetics & Stem Cells Authors: Torkamani A Tags: Trends Genet Source Type: research

Parallels between Mammalian Mechanisms of Monoallelic Gene Expression.
Abstract Different types of monoallelic gene expression are present in mammals, some of which are highly flexible, whereas others are more rigid. These include allelic exclusion at antigen receptor loci, the expression of olfactory receptor genes, genomic imprinting, X-chromosome inactivation, and random monoallelic expression (MAE). Although these processes play diverse biological roles, and arose through different selective pressures, the underlying epigenetic mechanisms show striking resemblances. Regulatory transcriptional events are important in all systems, particularly in the specification of MAE. Combined ...
Source: Trends in Genetics : TIG - September 11, 2018 Category: Genetics & Stem Cells Authors: Khamlichi AA, Feil R Tags: Trends Genet Source Type: research

Pimp My Ribosome: Ribosomal Protein Paralogs Specify Translational Control.
Abstract The ability of cells to grow and divide, differentiate and function, and even senesce is dependent on the fine-tuning of both gene and protein expression. Protein concentration in the cell is regulated not only at the transcriptional and post-translational levels, but also at the level of translation. Ribosomes, the molecular machines behind translation, were once considered to be an invariant driving force behind protein expression. However, studies over the past decade paint a rather different picture; namely, that ribosomes constitute an additional layer of regulatory control that might define which su...
Source: Trends in Genetics : TIG - September 5, 2018 Category: Genetics & Stem Cells Authors: Gerst JE Tags: Trends Genet Source Type: research

Transposons, p53 and Genome Security.
Abstract p53, the most commonly mutated tumor suppressor, is a transcription factor known to regulate proliferation, senescence, and apoptosis. Compelling studies have found that p53 may prevent oncogenesis through effectors that are unrelated to these canonical processes and recent findings have uncovered ancient roles for p53 in the containment of mobile elements. Together, these developments raise the possibility that some p53-driven cancers could result from unrestrained transposons. Here, we explore evidence linking conserved features of p53 biology to the control of transposons. We also show how p53-deficien...
Source: Trends in Genetics : TIG - September 5, 2018 Category: Genetics & Stem Cells Authors: Tiwari B, Jones AE, Abrams JM Tags: Trends Genet Source Type: research

RNA, Action through Interactions.
Abstract As transcription of the human genome is quite pervasive, it is possible that many novel functions of the noncoding genome have yet to be identified. Often the noncoding genome's functions are carried out by their RNA transcripts, which may rely on their structures and/or extensive interactions with other molecules. Recent technology developments are transforming the fields of RNA biology from studying one RNA at a time to transcriptome-wide mapping of structures and interactions. Here, we highlight the recent advances in transcriptome-wide RNA interaction analysis. These technologies revealed surprising v...
Source: Trends in Genetics : TIG - August 31, 2018 Category: Genetics & Stem Cells Authors: Nguyen TC, Zaleta-Rivera K, Huang X, Dai X, Zhong S Tags: Trends Genet Source Type: research