RESUMO
Variants of the histone H2A occupy distinct locations in the genome. There is relatively little known about the mechanisms responsible for deposition of specific H2A variants. Notable exceptions are chromatin remodelers that control the dynamics of H2A.Z at promoters. Here we review the steps that identified the role of a specific class of chromatin remodelers, including LSH and DDM1 that deposit the variants macroH2A in mammals and H2A.W in plants, respectively. The function of these remodelers in heterochromatin is discussed together with their multiple roles in genome stability.
Assuntos
Heterocromatina , Histonas , Animais , Histonas/genética , Histonas/metabolismo , Heterocromatina/genética , Cromatina , Regiões Promotoras Genéticas , Mamíferos/genética , Biologia , NucleossomosRESUMO
William Lawrence Tower's work on the evolution of the Colorado Potato Beetle (Leptinotarsa decemlineata), documenting the environmental induction of mutation and speciation, made him a leading figure in experimental genetics during the first decade of the 20th century. His research program served as a model for other experimental evolution studies seeking to demonstrate the environmental modification of inheritance. Tower enjoyed the support of influential figures in the field, despite well-known problems that plagued Tower's earlier academic career. The validity of his genetic work, and other findings reported by Tower, were later challenged. The Tower affair illustrates how questionable and possibly fraudulent scientific practices can be tolerated to explore certain experimental directions and theoretical frameworks, particularly at the frontier of expanding disciplines. When needed, those explorations can be forestalled or extinguished by exploiting conspicuous vulnerabilities of rogue practitioners. In Tower's case, both unrefuted allegations of scientific misconduct and personal problems dissolved his institutional support, leading to a swift ouster from academic science. Tower's downfall discredited soft inheritance and neo-Lamarckian conceptions in the field of experimental genetics, facilitating the discipline's embrace of a hard inheritance model that featured a hereditary material resistant to environmental modification.
Assuntos
Evolução Biológica , Besouros , Besouros/genética , Animais , História do Século XX , Genética/história , Estados UnidosRESUMO
The nuclear lamina in plant cells is composed of plant-specific proteins, including nuclear matrix constituent proteins (NMCPs), which have been postulated to be functional analogs of lamin proteins that provide structural integrity to the organelle and help stabilize the three-dimensional organization of the genome. Using genomic editing, we generated alleles for the three genes encoding NMCPs in cultivated tomato (Solanum lycopersicum) to determine if the consequences of perturbing the nuclear lamina in this crop species were similar to or distinct from those observed in the model Arabidopsis thaliana. Loss of the sole NMCP2-class protein was lethal in tomato but is tolerated in Arabidopsis. Moreover, depletion of NMCP1-type nuclear lamina proteins leads to distinct developmental phenotypes in tomato, including leaf morphology defects and reduced root growth rate (in nmcp1b mutants), compared with cognate mutants in Arabidopsis. These findings suggest that the nuclear lamina interfaces with different developmental and signaling pathways in tomato compared with Arabidopsis. At the subcellular level, however, tomato nmcp mutants resembled their Arabidopsis counterparts in displaying smaller and more spherical nuclei in differentiated cells. This result argues that the plant nuclear lamina facilitates nuclear shape distortion in response to forces exerted on the organelle within the cell.
Assuntos
Arabidopsis , Solanum lycopersicum , Lâmina Nuclear/metabolismo , Solanum lycopersicum/genética , Arabidopsis/metabolismo , Núcleo Celular/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Associadas à Matriz Nuclear/metabolismoRESUMO
BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused high inpatient mortality and morbidity throughout the world. COVID-19 convalescent plasma (CCP) has been utilized as a potential therapy for patients hospitalized with coronavirus disease 2019 (COVID-19) pneumonia. This study evaluated the outcomes of hospitalized patients with COVID-19 treated with CCP in a prospective, observational, multicenter trial. METHODS: From April through August 2020, hospitalized patients with COVID-19 at 16 participating hospitals in Colorado were enrolled and treated with CCP and compared with hospitalized patients with COVID-19 who were not treated with convalescent plasma. Plasma antibody levels were determined following the trial, given that antibody tests were not approved at the initiation of the trial. CCP-treated and untreated hospitalized patients with COVID-19 were matched using propensity scores followed by analysis for length of hospitalization and inpatient mortality. RESULTS: A total of 542 hospitalized patients with COVID-19 were enrolled at 16 hospitals across the region. A total of 468 hospitalized patients with COVID-19 were entered into propensity score matching with 188 patients matched for analysis in the CCP-treatment and control arms. Fine-Gray models revealed increased length of hospital stay in CCP-treated patients and no change in inpatient mortality compared with controls. In subgroup analysis of CCP-treated patients within 7 days of admission, there was no difference in length of hospitalization and inpatient mortality. CONCLUSIONS: These data show that treatment of hospitalized patients with COVID-19 treated with CCP did not significantly improve patient hospitalization length of stay or inpatient mortality.
Assuntos
COVID-19 , COVID-19/terapia , Humanos , Imunização Passiva/efeitos adversos , Estudos Prospectivos , SARS-CoV-2 , Resultado do Tratamento , Soroterapia para COVID-19RESUMO
OBJECTIVES: The development of accelerated approval programs for high morbidity and unmet need conditions has driven the use of single-arm studies in drug development. Regulatory and health technology assessment (HTA) agencies are recognizing that high-quality external control arms (ECAs), built using real-world data, can reduce uncertainties arising from single-arm studies. This review compared 7 case studies of regulatory and HTA agencies' evaluations of oncology ECAs. METHODS: Food and Drug Administration multidisciplinary reviews for oncology submissions from 2014 to 2021 were screened to identify 7 cases (2 blinatumomab indications, avelumab, and erdafitinib, entrectinib, trastuzumab deruxtecan, and idecabtagene vicleucel) with ECAs to support efficacy claims. Regulatory (Food and Drug Administration, European Medicines Agency, Health Canada) and HTA (pan-Canadian Oncology Drug Review, National Institute for Health and Care Excellence, Federal Joint Committee, Haute Autorité de Santé, and Pharmaceutical Benefits Advisory Committee) submissions for these cases were reviewed. The decision makers' ECA critiques and the level of influence on the decision were analyzed and categorized. RESULTS: Across case studies, selection bias and confounding were the most common ECA critiques. Nevertheless, agreement in critiques between and among regulators and HTA bodies was low. ECA influence on agencies' decisions also varied. CONCLUSIONS: Evaluating the same ECA evidence, agencies focused on methodologic issues (ie, selection bias and confounding), but were often not aligned on their critiques. Further research is needed to fully characterize how agencies evaluate ECAs. This study is a first step in critically evaluating agencies' critiques of ECAs and highlights the need for future guidance development around ECA design and generation.
Assuntos
Oncologia , Avaliação da Tecnologia Biomédica , Humanos , Estados Unidos , Canadá , PesquisaRESUMO
Defects in the nuclear lamina of animal cell nuclei have dramatic effects on nuclear structure and gene expression as well as diverse physiological manifestations. We report that deficiencies in CROWDED NUCLEI (CRWN), which are candidate nuclear lamina proteins in Arabidopsis (Arabidopsis thaliana), trigger widespread changes in transcript levels and whole-plant phenotypes, including dwarfing and spontaneous cell death lesions. These phenotypes are caused in part by ectopic induction of plant defense responses via the salicylic acid pathway. Loss of CRWN proteins induces the expression of the salicylic acid biosynthetic gene ISOCHORISMATE SYNTHASE1, which leads to spontaneous defense responses in crwn1 crwn2 and crwn1 crwn4 mutants, which are deficient in two of the four CRWN paralogs. The symptoms of ectopic defense response, including pathogenesis marker gene expression and cell death, increase in older crwn double mutants. These age-dependent effects are postulated to reflect an increase in nuclear dysfunction or damage over time, a phenomenon reminiscent of aging effects seen in animal nuclei and in some human laminopathy patients.
Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Transferases Intramoleculares/metabolismo , Proteínas Nucleares/metabolismo , Ácido Salicílico/metabolismo , Arabidopsis/genética , Arabidopsis/imunologia , Proteínas de Arabidopsis/genética , Botrytis , Morte Celular , Mapeamento Cromossômico , Regulação da Expressão Gênica de Plantas , Transferases Intramoleculares/genética , Mutação , Proteínas Nucleares/genética , Fenótipo , Pseudomonas syringaeRESUMO
Dihydrodipicolinate reductase (DHDPR) catalyses the second reaction in the diaminopimelate pathway of lysine biosynthesis in bacteria and plants. In contrast with the tetrameric bacterial DHDPR enzymes, we show that DHDPR from Vitis vinifera (grape) and Selaginella moellendorffii are dimeric in solution. In the present study, we have also determined the crystal structures of DHDPR enzymes from the plants Arabidopsis thaliana and S. moellendorffii, which are the first dimeric DHDPR structures. The analysis of these models demonstrates that the dimer forms through the intra-strand interface, and that unique secondary features in the plant enzymes block tetramer assembly. In addition, we have also solved the structure of tetrameric DHDPR from the pathogenic bacteria Neisseria meningitidis Measuring the activity of plant DHDPR enzymes showed that they are much more prone to substrate inhibition than the bacterial enzymes, which appears to be a consequence of increased flexibility of the substrate-binding loop and higher affinity for the nucleotide substrate. This higher propensity to substrate inhibition may have consequences for ongoing efforts to increase lysine biosynthesis in plants.
Assuntos
Proteínas de Bactérias/química , Di-Hidrodipicolinato Redutase/química , Ácidos Picolínicos/química , Proteínas de Plantas/química , Vitis/enzimologia , Motivos de Aminoácidos , Arabidopsis/química , Arabidopsis/enzimologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sítios de Ligação , Coenzimas/química , Coenzimas/metabolismo , Cristalografia por Raios X , Di-Hidrodipicolinato Redutase/genética , Di-Hidrodipicolinato Redutase/metabolismo , Expressão Gênica , Cinética , Lisina/biossíntese , Modelos Moleculares , NAD/química , NAD/metabolismo , NADP/química , NADP/metabolismo , Neisseria meningitidis/química , Neisseria meningitidis/enzimologia , Ácidos Picolínicos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Multimerização Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Selaginellaceae/química , Selaginellaceae/enzimologia , Especificidade da Espécie , Especificidade por Substrato , Vitis/químicaRESUMO
Two recent reports, including one by Reinders and colleagues (pp. 939-950) in the April 15, 2009, issue of Genes & Development, describe the construction of Arabidopsis recombinant inbred populations that maximize epigenetic rather than genetic variation. The distribution and behavior of phenotypic variation in these populations suggest that stable epialleles can control complex quantitative traits. However, stochastic epimutation and transposon movement in these populations present some unexpected technical hurdles to implementing quantitative epigenetic analysis.
Assuntos
Arabidopsis/genética , Epigênese Genética , Variação Genética , Elementos de DNA Transponíveis , Instabilidade Genômica , Endogamia , Mutação , FenótipoRESUMO
To evaluate the impact of semantic information elicited by labels, participants learned to identify or use novel graspable objects associated with novel actions. We identified each object/action pair with labels that elicited visual form or action semantics and varied the congruence between the label's information and the visual form or action of novel objects. In Experiment 1, participants named objects, and in Experiment 2 they produced the action associated with objects. Generally, congruent labels facilitated performance. Furthermore, for participants who learned incongruent associations, the visual form and semantic information elicited by labels influenced performance in opposite patterns. These findings support the notion that naming may be required before actions are produced when object/action associations are novel. Our findings further support the notion that links between the structural properties of objects and their actions may already be stronger than the links between verbal labels and actions in novel object/action associations.
Assuntos
Atividade Motora/fisiologia , Desempenho Psicomotor/fisiologia , Semântica , Percepção Visual/fisiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto JovemRESUMO
BACKGROUND: Plant nuclei superficially resemble animal and fungal nuclei, but the machinery and processes that underlie nuclear organization in these eukaryotic lineages appear to be evolutionarily distinct. Among the candidates for nuclear architectural elements in plants are coiled-coil proteins in the NMCP (Nuclear Matrix Constituent Protein) family. Using genetic and cytological approaches, we dissect the function of the four NMCP family proteins in Arabidopsis encoded by the CRWN genes, which were originally named LINC (LITTLE NUCLEI). RESULTS: CRWN proteins are essential for viability as evidenced by the inability to recover mutants that have disruptions in all four CRWN genes. Mutants deficient in different combinations of the four CRWN paralogs exhibit altered nuclear organization, including reduced nuclear size, aberrant nuclear shape and abnormal spatial organization of constitutive heterochromatin. Our results demonstrate functional diversification among CRWN paralogs; CRWN1 plays the predominant role in control of nuclear size and shape followed by CRWN4. Proper chromocenter organization is most sensitive to the deficiency of CRWN4. The reduction in nuclear volume in crwn mutants in the absence of a commensurate reduction in endoreduplication levels leads to an increase in average nuclear DNA density. CONCLUSIONS: Our findings indicate that CRWN proteins are important architectural components of plant nuclei that play diverse roles in both heterochromatin organization and the control of nuclear morphology.
Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Núcleo Celular/genética , Heterocromatina/genética , Proteínas Nucleares/genética , Sequência de Aminoácidos , Arabidopsis/citologia , Arabidopsis/metabolismo , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/metabolismo , Núcleo Celular/metabolismo , Citometria de Fluxo , Heterocromatina/metabolismo , Hibridização in Situ Fluorescente , Dados de Sequência Molecular , Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Filogenia , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Septic arthritis is a rheumatologic emergency as joint destruction occurs rapidly and can lead to significant morbidity and mortality. Accurate diagnosis can be particularly challenging in patients with underlying inflammatory joint disease. This review outlines the risk factors for septic arthritis and summarizes the causative bacterial organisms. We highlight advances in antibiotic management with a focus on new drugs for methicillin-resistant Staphylococcus aureus (MRSA) and discuss the use of adjunctive therapies for treatment of septic arthritis in adults.
Assuntos
Antibacterianos/uso terapêutico , Artrite Infecciosa/tratamento farmacológico , Infecções Bacterianas/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Acetamidas/uso terapêutico , Artrite Infecciosa/diagnóstico , Artrite Infecciosa/microbiologia , Infecções Bacterianas/complicações , Infecções Bacterianas/diagnóstico , Cefalosporinas/uso terapêutico , Daptomicina/uso terapêutico , Quimioterapia Combinada , Humanos , Linezolida , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Oxazolidinonas/uso terapêutico , Fatores de Risco , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Resultado do Tratamento , Virginiamicina/uso terapêutico , CeftarolinaRESUMO
Regulation of cytosine methylation in the plant genome is of pivotal in determining the epigenetic states of chromosome regions. Relative tolerance of plant to deficiency in cytosine methylation provides unparalleled opportunities to study the mechanism for regulation of cytosine methylation. The Decrease in DNA Methylation 1 (DDM1) of Arabidopsis thaliana is one of the best characterized plant epigenetic regulators that are necessary for maintenance of cytosine methylation in genomic DNA. Although cytosine methylation could affect various aspects of plant growth and development including those related to agricultural importance, orthologs of DDM1 in plants other than Arabidopsis has not been studied in detail. In this study, we identified two rice genes with similarity to Arabidopsis DDM1 and designated them OsDDM1a and OsDDM1b. Both of the rice DDM1 homologs are transcribed during development and their amino acid sequences are 93 % identical to each other. Transgenic rice lines expressing the OsDDM1a cDNA in the antisense orientation exhibited genomic DNA hypomethylation. In those lines, repeated sequences were more severely affected than a single copy sequence as is the case in Arabidopsis ddm1 mutants. Transcripts derived from endogenous transposon-related loci were up-regulated in the antisense OsDDM1 lines, opening a possibility to identify and utilize potentially active transposons for rice functional genomics.
Assuntos
Proteínas de Ligação a DNA/genética , Oryza/genética , Proteínas de Plantas/genética , Fatores de Transcrição/genética , Sequência de Aminoácidos , Sequência Conservada , Metilação de DNA , Proteínas de Ligação a DNA/química , Genoma de Planta , Dados de Sequência Molecular , Filogenia , Proteínas de Plantas/química , Alinhamento de Sequência , Fatores de Transcrição/químicaRESUMO
Our knowledge of the mechanisms that specify and propagate epigenetic states of gene expression is expanding rapidly; however, the significance of variation in epigenetic states at the population level remains largely unexplored. Population epigenetics, emerging as an active subfield at the interface of molecular genetics, genomics, and population biology, addresses questions concerning the prevalence and importance of epigenetic variation in the natural world.
Assuntos
Epigênese Genética/genética , Genética Populacional , Alelos , Animais , Variação Genética/genética , HumanosRESUMO
The plant nuclear lamina utilizes distinct and highly divergent proteins to mediate chromatin interactions at the nuclear edge. In this issue of Developmental Cell, Tang et al. show that members of PNET2, a family of inner nuclear membrane proteins in Arabidopsis, are capable of binding histones and are involved in large-scale genome organization.
Assuntos
Núcleo Celular , Lâmina Nuclear , Cromatina , Histonas , Membrana NuclearRESUMO
Methylcytosine-binding proteins decipher the epigenetic information encoded by DNA methylation and provide a link between DNA methylation, modification of chromatin structure, and gene silencing. VARIANT IN METHYLATION 1 (VIM1) encodes an SRA (SET- and RING-associated) domain methylcytosine-binding protein in Arabidopsis thaliana, and loss of VIM1 function causes centromere DNA hypomethylation and centromeric heterochromatin decondensation in interphase. In the Arabidopsis genome, there are five VIM genes that share very high sequence similarity and encode proteins containing a PHD domain, two RING domains, and an SRA domain. To gain further insight into the function and potential redundancy among the VIM proteins, we investigated strains combining different vim mutations and transgenic vim knock-down lines that down-regulate multiple VIM family genes. The vim1 vim3 double mutant and the transgenic vim knock-down lines showed decreased DNA methylation primarily at CpG sites in genic regions, as well as repeated sequences in heterochromatic regions. In addition, transcriptional silencing was released in these plants at most heterochromatin regions examined. Interestingly, the vim1 vim3 mutant and vim knock-down lines gained ectopic CpHpH methylation in the 5S rRNA genes against a background of CpG hypomethylation. The vim1 vim2 vim3 triple mutant displayed abnormal morphological phenotypes including late flowering, which is associated with DNA hypomethylation of the 5' region of FWA and release of FWA gene silencing. Our findings demonstrate that VIM1, VIM2, and VIM3 have overlapping functions in maintenance of global CpG methylation and epigenetic transcriptional silencing.
Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Metilação de DNA , Proteínas de Ligação a DNA/metabolismo , Fosfatos de Dinucleosídeos/metabolismo , Inativação Gênica , Arabidopsis/química , Arabidopsis/genética , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , DNA de Plantas/genética , DNA de Plantas/metabolismo , DNA Ribossômico/genética , DNA Ribossômico/metabolismo , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Fosfatos de Dinucleosídeos/genética , Expressão Gênica , Regulação da Expressão Gênica de Plantas , Heterocromatina/genética , Heterocromatina/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Família Multigênica , Mutação , Estrutura Terciária de Proteína , RNA Ribossômico 5S/genética , RNA Ribossômico 5S/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
The periphery in animal nuclei is generally considered to be a transcriptionally repressive environment. Recent studies indicate that chromatin-based mechanisms establish a similar situation in plant nuclei. We demonstrated recently that the loss of CRWN nuclear lamina proteins in Arabidopsis leads to the misregulation of a group of genes involved in plant defense. How this defense response is triggered is largely unknown. Here, we briefly review recent findings that identify several layers of chromatin-based regulation responsible for this response. Further, we introduce new data suggesting that histone H3 lysine 27 tri-methylation levels are reduced in the absence of CRWNs near genes encoding transcription factors regulating SA biosynthesis, providing an explanation for SA induction. These discoveries begin to uncover the interplay between nuclear architecture and stress response in plants.
Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Cromatina/metabolismo , Proteínas Nucleares/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Cromatina/genética , Regulação da Expressão Gênica de Plantas , Histonas/metabolismo , Proteínas Nucleares/genética , Fatores de Transcrição/metabolismoRESUMO
Plants lack lamin proteins but contain a class of coiled-coil proteins that serve as analogues to form a laminal structure at the nuclear periphery. These nuclear matrix constituent proteins (NMCPs) play important roles in regulating nuclear morphology and are partitioned into two distinct groups. We investigated Arabidopsis NMCPs (called CRWNs) to study the interrelationship between the three NMCP1-type paralogues (CRWN1, 2, and 3) and the lone NMCP2-type paralogue, CRWN4. An examination of crwn mutants using protein immunoblots demonstrated that CRWN4 abundance depends on the presence of the NMCP1-type proteins, particularly CRWN1. The possibility that CRWN4 is coimported into the nucleus with nuclear localization signal (NLS)-bearing paralogues in the NMCP1-clade was discounted based on recovery of a crwn4-2 missense allele that disrupts a predicted NLS and lowers the abundance of CRWN4 in the nucleus. Further, a screen for mutations that suppress the effects of the crwn4-2 mutation led to the discovery of a missense allele, impa-1G146E, in one of the nine importin-α genes in the Arabidopsis genome. Our results indicate that the CRWN4 carries a functional NLS that interacts with canonic nuclear import machinery. Once imported, the level of CRWN4 within the nucleus is modulated by the abundance of NMCP1 proteins.
Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Matriz Nuclear/metabolismo , Proteínas Nucleares/metabolismo , Motivos de Aminoácidos , Sequência de Aminoácidos , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Genes Supressores , Loci Gênicos , Mutação/genética , Sinais de Localização Nuclear/metabolismo , Proteínas Nucleares/química , Proteínas Nucleares/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Homologia de Sequência de AminoácidosRESUMO
Divergence in gene expression is of interest because it generates molecular markers for phenotypic variation, potentially including the causes underlying this variation. Alteration of gene expression patterns can have a direct genetic (or epigenetic) basis in cis regulatory polymorphism or can be indirectly regulated by trans-acting factors. Expression mapping studies have begun to reveal the local (suggesting cis) and distant (usually trans) patterns of inheritance of genetic variation that underlies transcriptional polymorphism. The molecular basis that contributes to transcriptional divergence is, however, largely unknown especially for genes under selection that might influence phenotype. Additional genome-wide empirical data from many related organisms are required to dissect cis-, trans-, and cis x trans- dependent sources of variation in gene expression to provide a better understanding of the evolution of transcriptional regulatory networks.
Assuntos
Epigênese Genética , Sequências Reguladoras de Ácido Nucleico/genética , Arabidopsis/genética , Variação Genética , Polimorfismo de Nucleotídeo Único/genética , Locos de Características QuantitativasRESUMO
Epigenetic variation is a potential source of genomic and phenotypic variation among different individuals in a population, and among different varieties within a species. We used a two-tiered approach to identify naturally occurring epigenetic alleles in the flowering plant Arabidopsis: a primary screen for transcript level polymorphisms among three strains (Col, Cvi, Ler), followed by a secondary screen for epigenetic alleles. Here, we describe the identification of stable, meiotically transmissible epigenetic alleles that correspond to one member of a previously uncharacterized non-LTR retroposon family, which we have designated Sadhu. The pericentromeric At2g10410 element is highly expressed in strain Col, but silenced in Ler and 18 other strains surveyed. Transcription of this locus is inversely correlated with cytosine methylation and both the expression and DNA methylation states map in a Mendelian manner to stable cis-acting variation. The silent Ler allele can be converted by the epigenetic modifier mutation ddm1 to a meiotically stable expressing allele with an identical primary nucleotide sequence, demonstrating that the variation responsible for transcript level polymorphism among Arabidopsis strains is epigenetic. We extended our characterization of the Sadhu family members and show that different elements are subject to both genetic and epigenetic variation in natural populations. These findings support the view that an important component of natural variation in retroelements is epigenetic.