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1.
Ann Hematol ; 99(10): 2279-2288, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32772141

RESUMO

Sickle cell disease (SCD) is a monogenic disease characterized by multisystem morbidity and highly variable clinical course. Inter-individual variability in hemoglobin F (HbF) levels is one of the main modifiers that account for the clinical heterogeneity in SCD. HbF levels are affected by, among other factors, single nucleotide polymorphisms (SNPs) at the BCL11A gene and the HBS1L-MYB intergenic region and Xmn1 gene. Our aim was to investigate HbF-enhancer haplotypes at these loci to obtain a first overview of the genetic situation of SCD patients in Egypt and its impact on the severity of the disease. The study included 100 SCD patients and 100 matched controls. Genotyping of BCL11A (rs1886868 C/T), HBS1L-MYB (rs9389268 A/G) and Xmn1 γG158 (rs7842144 C/T) SNPs showed no statistically significant difference between SCD patients and controls except for the hetero-mutant genotypes of BCL11A which was significantly higher in SCD patients compared with controls. Baseline HbF levels were significantly higher in those with co-inheritance of polymorphic genotypes of BCL11A + HSB1L-MYB and BCL11A + Xmn1. Steady-state HbF levels, used as an indicator of disease severity, were significantly higher in SCD-Sß patients having the polymorphic genotypes of HSB1L-MYB. Fold change of HbF in both patient groups did not differ between those harboring the wild and the polymorphic genotypes of the studied SNPs. In conclusion, BCL11A, HSB1L, and Xmn1 genetic polymorphisms had no positive impact on baseline HbF levels solely but had if coexisted. Discovery of the molecular mechanisms controlling HbF production could provide a more effective strategy for HbF induction.


Assuntos
Anemia Falciforme/genética , DNA Intergênico/genética , Hemoglobina Fetal/análise , Proteínas de Ligação ao GTP/genética , Genes myb , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas/genética , Proteínas Repressoras/genética , gama-Globinas/genética , Adolescente , Alelos , Anemia Falciforme/sangue , Anemia Falciforme/etnologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos Transversais , Desoxirribonucleases de Sítio Específico do Tipo II , Egito , Feminino , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , Polimorfismo de Fragmento de Restrição , Adulto Jovem
2.
Ann Hematol ; 99(7): 1453-1463, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32447424

RESUMO

Fetal hemoglobin (HbF) ameliorates clinical severity of sickle cell anemia (SCA). The major loci regulating HbF levels are HBB cluster, BCL11A, and HMIP-2 (HBS1L-MYB). However, the impact of noncoding single-nucleotide polymorphisms (SNPs) in these loci on clinical outcomes and their functional role on regulating HbF levels should be better elucidated. Therefore, we performed comprehensive association analyses of 14 noncoding SNPs in five loci with HbF levels and with clinical outcomes in a cohort of 250 children with SCA from Southeastern Brazil, and further performed functional annotation of these SNPs. We found SNPs independently associated with HbF levels: rs4671393 in BCL11A (ß-coefficient = 0.28), rs9399137 in HMIP-2A (ß-coefficient = 0.16), and rs4895441 in HMIP-2B (ß-coefficient = 0.15). Patients carrying minor (HbF-boosting) alleles for rs1427407, rs93979137, rs4895441, rs9402686, and rs9494145 showed reduced count of reticulocytes (p < 0.01), while those carrying the T allele of rs9494145 showed lower white blood cell count (p = 0.002). Carriers of the minor allele for rs9402686 showed higher peripheral saturation of oxygen (p = 0.002). Patients carrying minor alleles in BCL11A showed lower risk of transfusion incidence rate ratio (IRR ≥ 1.3; p < 0.0001). This effect was independent of HbF effect (p = 0.005). Carriers of minor alleles for rs9399137 and rs9402686 showed lower risk of acute chest syndrome (IRR > 1.3; p ≤ 0.01). Carriers of the reference allele for rs4671393 showed lower risk of infections (IRR = 1.16; p = 0.01). In conclusion, patients carrying HbF-boosting alleles of BCL11A and HMIP-2 were associated with milder clinical phenotypes. Higher HbF concentration may underlie this effect.


Assuntos
Anemia Falciforme/diagnóstico , Anemia Falciforme/genética , Hemoglobina Fetal/metabolismo , Proteínas de Ligação ao GTP/genética , Genes myb , Polimorfismo de Nucleotídeo Único , Proteínas Repressoras/genética , Alelos , Anemia Falciforme/sangue , Anemia Falciforme/epidemiologia , Brasil/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Hemoglobina Fetal/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Lactente , Recém-Nascido , Masculino , Prognóstico , Estudos Retrospectivos
3.
Int J Mol Sci ; 20(19)2019 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-31569557

RESUMO

As an important nongrain crop, the growth and yield of potato (Solanum tuberosum L.) is often affected by an unfavorable external environment in the process of cultivation. The MYB family is one of the largest and most important gene families, participating in the regulation of plant growth and development and response to abiotic stresses. Several MYB genes in potato that regulate anthocyanin synthesis and participate in abiotic stress responses have been identified. To identify all Solanum tuberosum L. MYB (StMYB) genes involved in hormone or stress responses to potentially regulate potato growth and development, we identified the MYB gene family at the genome-wide level. In this work, 158 StMYB genes were found in the potato genome. According to the amino acid sequence of the MYB domain and gene structure, the StMYB genes were divided into R2R3-MYB and R1R2R3-MYB families, and the R2R3-MYB family was divided into 20 subgroups (SGs). The expression of 21 StMYB genes from different SGs in roots, stems, leaves, flowers, shoots, stolons, young tubers, and mature tubers was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The expression patterns of StMYB genes in potatoes treated with abscisic acid (ABA), indole-3-acetic acid (IAA), gibberellin acid 3 (GA3), NaCl, mannitol, and heat were also measured. We have identified several potential candidate genes that regulate the synthesis of potato flavonoids or participate in hormone or stress responses. This work provides a comprehensive understanding of the MYB family in potato and will lay a foundation for the future investigation of the potential functions of StMYB genes in the growth and development of potato.


Assuntos
Genes myb , Família Multigênica , Solanum tuberosum/genética , Evolução Molecular , Genoma de Planta , Estudo de Associação Genômica Ampla , Genômica/métodos , Filogenia , Desenvolvimento Vegetal/genética , Reguladores de Crescimento de Planta/metabolismo , Proteínas de Plantas/genética , Transporte Proteico , Solanum tuberosum/classificação , Estresse Fisiológico
4.
Plant Sci ; 286: 28-36, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31300139

RESUMO

MYB family genes act as important regulators modulating the response to abiotic stress in plants. However, much less is known about MYB proteins in cotton. Here, we found that a cotton MYB gene, GhMYB73, was induced by NaCl and abscisic acid (ABA). Silencing GhMYB73 expression in cotton increased sensitivity to salt stress. The cotyledon greening rate of Arabidopsis thaliana over-expressing GhMYB73 under NaCl or mannitol treatment was significantly enhanced during the seedling germination stage. What's more, several osmotic stress-induced genes, such as AtNHX1, AtSOS3 and AtP5CS1, were more highly induced in the over-expression lines than in wild type under salt treatment, supporting the hypothesis that GhMYB73 contributes to salinity tolerance by improving osmotic stress resistance. Arabidopsis lines over-expressing GhMYB73 had superior germination and cotyledon greening under ABA treatment, and some abiotic stress-induced genes involved in ABA pathways (AtPYL8, AtABF3, AtRD29B and AtABI5), had increased transcription levels under salt-stress conditions in these lines. Furthermore, we found that GhMYB73 physically interacts with GhPYL8 and AtPYL8, suggesting that GhMYB73 regulates ABA signaling during salinity stress response. Taken together, over-expression of GhMYB73 significantly increases tolerance to salt and ABA stress, indicating that it can potentially be used in transgenic technology approaches to improve cotton salt tolerance.


Assuntos
Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Gossypium/fisiologia , Proteínas de Plantas/genética , Estresse Salino/genética , Fatores de Transcrição/genética , Arabidopsis/genética , Inativação Gênica , Genes myb , Gossypium/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Tolerância ao Sal/genética , Fatores de Transcrição/metabolismo
5.
BMC Plant Biol ; 19(1): 169, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31035916

RESUMO

BACKGROUND: Lycium ruthenicum Murray is an important economic plant in China and contains higher levels of anthocyanins in its fruits than other Lyciums. However, the genetic mechanism of anthocyanin production in this plant is unknown. RESULTS: Based on previous transcriptome analysis, LrAN2 and LbAN2, encoding MYB transcription factors, were isolated from L. ruthenicum and L. barbarum, respectively. Both genes contained two introns, encoded 257 amino acids with two-Aa difference, and carried the unabridged HTH-MYB, MYB-like DNA-binding, and SANT domains. In the phylogenetic trees, LrAN2 and LbAN2 were found to be closely related to NtAN2, which regulates anthocyanin biosynthesis in tobacco. Overexpression of LrAN2 and LbAN2 induced anthocyanin biosynthesis in all tissues of tobacco. The anthocyanin content in the leaves of transgenic lines with LbAN2 was lower than LrAN2. It indicated that the function of LbAN2 was weaker than LrAN2. The AN2 transcript could be detected only in the fruits of L. ruthenicum and increased during fruit development, accompanied by anthocyanin accumulation. In natural population, the alleles LrAN2 and LrAN2 were associated strictly with L. ruthenicum and L. barbarum, respectively. Moreover, an AN2 genetic diversity study suggested that Lyciums with yellow, white, purple, and jujube red fruits were derived from L. ruthenicum. CONCLUSIONS: Two AN2 alleles, from L. ruthenicum and L. barbarum, were functional MYB transcriptor regulating anthocyanin biosynthesis. The functional diversity and high expression level of LrAN2 could be the reason for high anthocyanin content in the fruit of L. ruthenicum. Lyciums with yellow, white, purple, and jujube red fruits were derived from L. ruthenicum based on AN2 sequence diversity. The results may be advantageous in identifying new varieties and breeding new cultivars.


Assuntos
Antocianinas/biossíntese , Genes de Plantas , Lycium/genética , Proteínas de Plantas/genética , Fatores de Transcrição/genética , Alelos , China , Frutas/genética , Frutas/crescimento & desenvolvimento , Genes myb , Variação Genética , Lycium/crescimento & desenvolvimento , Lycium/metabolismo , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo
6.
PLoS One ; 14(3): e0203014, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30860996

RESUMO

Rosa roxburghii Tratt (Rosaceae) has a fruit that is flavorful, economically valuable, and highly nutritious, providing numerous health benefits. Myeloblastosis (MYB) proteins play key roles in the development and fruit quality of R. roxburghii. However, there is little available genomic and transcriptomic information for R. roxburghii. Here, a normalized cDNA library was constructed from five tissues, including the stem, leaf, flower, young fruit, and mature fruit, using the Illumina HiSeq 3000 platform. De novo assembly was performed, and 470.66 million clean reads were obtained. In total, 63,727 unigenes, with an average GC content of 42.08%, were discovered, 60,406 of which were annotated. In addition, 9,354 unigenes were assigned to Gene Ontology categories, and 20,202 unigenes were assigned to 25 Eukaryotic Ortholog Groups. Additionally, 19,508 unigenes were classified into 140 pathways of the Kyoto Encyclopedia of Genes and Genomes database. Based on the transcriptome, 163 unigenes associated with MYBs were detected. Among these genes, 75 genes were significantly expressed in the various tissues, including 10 R1 MYB, 42 R2R3 MYB, one R1R2R3 MYB, three R4 MYB and 19 atypical MYB-like proteins. The expression levels of the 12 MYB genes randomly selected for quantitative real-time PCR analysis corroborated the RNA sequencing results. A total of 37,545 microsatellites were detected, with an average expressed sequence tag-simple sequence repeat frequency of 0.59 (37,545/63,727). This transcriptome data improves our understanding of the role of MYB in R. roxburghii and will be valuable for identifying genes of interest.


Assuntos
Genes de Plantas , Rosa/genética , China , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genes myb , Repetições de Microssatélites , Anotação de Sequência Molecular , Proteínas de Plantas/genética , RNA de Plantas/genética , RNA de Plantas/metabolismo , Rosa/metabolismo , Distribuição Tecidual , Fatores de Transcrição/genética
7.
Biochem Biophys Res Commun ; 512(1): 66-71, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-30862358

RESUMO

Drought is the most serious meteorological disaster affecting wheat production. Members of the R2R3-MYB gene subfamily play a crucial role in the regulation of the wheat drought stress response. In this study, the function of polyethylene glycol (PEG)-induced expression of the wheat R2R3-MYB gene TaSIM in response to drought stress was characterized. ß-Glucuronidase (GUS) histochemical staining revealed that the TaSIM promoter can drive the expression of the GUS gene in the flowers, roots, stems and rosette leaves. Moreover, TaSIM was expressed in the stamens, pistils, roots, stems and leaves of wheat. The TaSIM promoter contains a known stress-responsive cis-acting element and is inducible by stress, PEG and abscisic acid (ABA). Under drought stress, compared with wild-type (WT) Arabidopsis, transgenic Arabidopsis overexpressing TaSIM presented significantly lower leaf water loss rates and increased survival. Moreover, the content of soluble sugars and proline and the expression of stress-related genes (RD29A and RD22) in transgenic Arabidopsis overexpressing TaSIM were higher than those in WT Arabidopsis under drought stress. Our results indicate that TaSIM plays a positive role in the drought stress response and can be used as a candidate gene for the genetic engineering of wheat drought resistance.


Assuntos
Arabidopsis/genética , Arabidopsis/fisiologia , Secas , Genes de Plantas , Estresse Fisiológico/genética , Ácido Abscísico/metabolismo , Aclimatação/genética , Aclimatação/fisiologia , Regulação da Expressão Gênica de Plantas , Genes myb , Engenharia Genética , Reguladores de Crescimento de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/fisiologia , Plantas Geneticamente Modificadas , Prolina/metabolismo , Regiões Promotoras Genéticas , Açúcares/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/fisiologia , Triticum/genética , Triticum/fisiologia , Regulação para Cima
8.
New Phytol ; 221(4): 1919-1934, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30222199

RESUMO

Anthocyanin and proanthocyanidin (PA) accumulation is regulated by both myeloblastosis (MYB) activators and repressors, but little information is available on hierarchical interactions between the positive and negative regulators. Here, we report on a R2R3-MYB repressor in peach, designated PpMYB18, which acts as a negative regulator of anthocyanin and PA accumulation. PpMYB18 can be activated by both anthocyanin- and PA-related MYB activators, and is expressed both at fruit ripening and juvenile stages when anthocyanins or PAs, respectively, are being synthesized. The PpMYB18 protein competes with MYB activators for binding to basic Helix Loop Helixes (bHLHs), which develops a fine-tuning regulatory loop to balance PA and anthocyanin accumulation. In addition, the bHLH binding motif in the R3 domain and the C1 and C2 repression motifs in the C-terminus of PpMYB18 both confer repressive activity of PpMYB18. Our study also demonstrates a modifying negative feedback loop, which prevents cells from excess accumulation of anthocyanin and PAs, and serves as a model for balancing secondary metabolite accumulation at the transcriptional level.


Assuntos
Antocianinas/metabolismo , Genes de Plantas , Genes myb , Proteínas de Plantas/genética , Proantocianidinas/metabolismo , Prunus persica/genética , Proteínas Repressoras/genética , Sequência de Aminoácidos , Vias Biossintéticas/genética , Evolução Molecular , Regulação da Expressão Gênica de Plantas , Mutação/genética , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Ligação Proteica , Prunus persica/crescimento & desenvolvimento , Proteínas Repressoras/metabolismo , Transcrição Genética
9.
Ecotoxicol Environ Saf ; 170: 682-690, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30580162

RESUMO

R.communis L. has high capability to accumulate nickel which is a trace nutrient for higher plants and also an environmental contaminant causes toxicity related symptoms at higher concentrations. MicroRNAs (miRNAs) are known to be important modulators of responses against heavy metal stress for detoxification of the metal. In this study, we experimentally measured and validated the transcript levels of the seven heavy metal stress response-related miRNAs and the expression levels of target genes in both leaf and root tissues of R. communis L. subjected to three different concentrations of nickel stress via qRT-PCR quantification. The results demonstrated differential regulations of heavy metal stress-responsive miRNAs and their putative targets in both tissues in same stress treatments. This dynamic regulation suggest that regulatory processes differ between the tissues under nickel stress. Our data suggest that, miR838 was the most responsive to the Ni2+ stress. miR398 target gene Cu-Zn/SOD was found to be up-regulated in both root and leaf tissues. The relations between TCP and expression levels of miR159 and miR319 were also found statistically significant exclusive to leaf tissues. In leaf tissue, changes in miR395 level and its putative target genes, sulphate transporter and sulphate adenyltransferase gene were found in relation whereas, only expression level of sulphate transporter represented a statistically significant relation in root tissue. The sharp decrease in transcript levels of 2r3 myb gene at lower nickel dose suggest to investigate the role of r2r3 myb and the all MYB family members in primary and secondary metabolisms against nickel stress.


Assuntos
Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Metais Pesados/toxicidade , MicroRNAs/genética , Estresse Fisiológico/genética , Semente de Rícino , Genes myb/efeitos dos fármacos , Níquel , Folhas de Planta/genética , Raízes de Plantas/genética , Sulfato Adenililtransferase/genética , Transportadores de Sulfato/genética , Superóxido Dismutase-1/genética , Regulação para Cima
10.
Oral Dis ; 25(5): 1277-1282, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30269389

RESUMO

The presence of a translocation involving MYB and NFIB genes have been described in adenoid cystic carcinoma (AdCC) from different anatomical regions. However, the exact frequency of this genetic event and its prognostic impact for patient survival remain obscure. The aim of this study was to carry out a systematic review to address the prevalence and the prognostic potential of t(6;9)(MYB-NFIB) in head and neck AdCC. Quantitative analysis was done to determine the prevalence of the translocation. A total of 1,107 articles were initially retrieved with 36 remaining for data extraction. The prevalence of t(6;9)(MYB-NFIB) varied significantly (16%-100%), especially due to methodological heterogeneity among studies. A total of 11 studies attempted to determine the prognostic importance of the translocation, but no study found any significant association with survival rates; only three studies observed a significant association with age, sex, tumour location and the presence of recurrences and metastases. The prevalence of t(6;9)(MYB-NFIB) in head and neck AdCC varies according to the laboratorial methods used, and the best evidence available demonstrates that t(6;9)(MYB-NFIB) does not seem to be a prognostic determinant.


Assuntos
Carcinoma Adenoide Cístico/genética , Neoplasias de Cabeça e Pescoço/genética , Recidiva Local de Neoplasia/genética , Proteínas de Fusão Oncogênica/genética , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Carcinoma Adenoide Cístico/metabolismo , Genes myb , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Hibridização in Situ Fluorescente , Fatores de Transcrição NFI , Prevalência , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa
11.
Planta ; 249(3): 861-877, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30448862

RESUMO

MAIN CONCLUSION: Four R3 MYB genes were cloned and identified from Platanus acerifolia and analysed according to endogenous gene expression profiles, protein-protein interaction patterns, phenotypic effects and related gene expression profiles in transgenic Arabidopsis, suggesting that London plane R3 MYB genes inhibit trichome formation in Arabidopsis. The CPC-like MYB transcription factors including CAPRICE (CPC), TRIPTYCHON (TRY), ENHANCER OF TRY AND CPC 1, 2 and 3 (ETC1, ETC2 and ETC3), TRICHOMELESS1 (TCL1) and TRICHOMELESS2(TCL2) play important roles in controlling trichome patterning in Arabidopsis. In this study, four sequences homologous with the Arabidopsis CPC family were identified from London plane and named PaTRY, PaCPC-like1, PaCPC-like2 and PaCPC-like3. Over-expression of PaTRY, PaCPC-like1, PaCPC-like2 and PaCPC-like3 in Arabidopsis resulted in glabrous phenotypes. In addition, expression of endogenous GL2, GL1, MYB23, TTG2 and a set of R3 MYB-encoding genes was markedly reduced. Furthermore, the protein products of PaTRY, PaCPC-like1, PaCPC-like2 and PaCPC-like3 were shown to interact with PaGL3 in yeast two-hybrid assays. Together, these results likely suggest that the mechanisms of trichome regulation in London plane have similarities with those in Arabidopsis.


Assuntos
Genes de Plantas/fisiologia , Genes myb/fisiologia , Magnoliopsida/genética , Proteínas de Plantas/fisiologia , Fatores de Transcrição/fisiologia , Tricomas/crescimento & desenvolvimento , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Clonagem Molecular , Genes de Plantas/genética , Genes myb/genética , Microscopia Eletrônica de Varredura , Mutagênese Sítio-Dirigida , Filogenia , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/ultraestrutura , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Reação em Cadeia da Polimerase em Tempo Real , Alinhamento de Sequência , Fatores de Transcrição/genética , Transcriptoma , Tricomas/genética , Tricomas/ultraestrutura , Técnicas do Sistema de Duplo-Híbrido
12.
PLoS One ; 13(12): e0207534, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30517137

RESUMO

Drought is the most significant environmental stress for agricultural production worldwide, and tremendous efforts have been made to improve crop yield under the increasing water scarcity. Transcription factors are major players in the regulation of water stress-related genes in plants. Recently, different MYB transcription factors were characterized for their involvement in drought response. A sugarcane R2R3-MYB gene (ScMYBAS1) and its four alternative forms of transcript (ScMYAS1-2, ScMYBAS1-3, ScMYBAS1-4 and ScMYBAS1-5) were identified in this study. The subcellular localization, in Nicotiniana benthamiana, of the TFs fused in frame with GFP revealed that ScMYBAS1-2-GFP and ScMYBAS1-3-GFP were observed in the nucleus. The overexpression of ScMYBAS1-2 and ScMYBAS1-3 spliced transcripts in rice promoted change in plant growth under both well-watered and drought conditions. The ScMYBAS1-2 and ScMYBAS1-3 transgenic lines revealed a higher relative water content (RWC) compared to the wild type before maximum stress under drought conditions. The ScMYBAS1-2 transgenic lines showed a reduction in biomass (total dry weight). Conversely, ScMYBAS1-3 showed an increased biomass (total dry weight) relative to the wild-type. The overexpression of ScMYBAS1-3 in rice transgenic lines showed involvement with drought tolerance and biomass and, for this reason, was considered a good target for plant transformation, particularly for use in developing genotypes with drought tolerance and biomass accumulation.


Assuntos
Proteínas Oncogênicas v-myb/genética , Oryza/genética , Saccharum/genética , Processamento Alternativo/genética , Biomassa , Secas , Regulação da Expressão Gênica de Plantas/genética , Genes myb/genética , Proteínas de Plantas , Plantas Geneticamente Modificadas/genética , Estresse Fisiológico/genética , Fatores de Transcrição/genética
13.
BMC Genomics ; 19(1): 881, 2018 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-30522435

RESUMO

BACKGROUND: The eukaryotic unicellular protist Plasmodiophora brassicae is an endocellular parasite of cruciferous plants. In host cortical cells, this protist develops a unicellular structure that is termed the plasmodium. The plasmodium is actually a multinucleated cell, which subsequently splits and forms resting spores. The mechanism for the growth of this endocellular parasite in host cell is unclear. RESULTS: Here, combining de novo genome sequence and transcriptome analysis of strain ZJ-1, we identified top five significant enriched KEGG pathways of differentially expressed genes (DEGs), namely translation, cell growth and death, cell communication, cell motility and cancers. We detected 171 proto-oncogenes from the genome of P. brassicae that were implicated in cancer-related pathways, of which 46 were differential expression genes. Three predicted proto-oncogenes (Pb-Raf1, Pb-Raf2, and Pb-MYB), which showed homology to the human proto-oncogenes Raf and MYB, were specifically activated during the plasmodial growth in host cortical cells, demonstrating their involvement in the multinucleate development stage of the unicellular protist organism. Gene networks involved in the tumorigenic-related signaling transduction pathways and the activation of 12 core genes were identified. Inhibition of phosphoinositol-3-kinase relieved the clubroot symptom and significantly suppressed the development process of plasmodia. CONCLUSIONS: Proto-oncogene-related regulatory mechanisms play an important role in the plasmodial growth of P. brassicae.


Assuntos
Genoma de Protozoário , Plasmodioforídeos/genética , Proto-Oncogenes/genética , Sequência de Aminoácidos , Brassica napus/metabolismo , Brassica napus/parasitologia , Perfilação da Expressão Gênica , Genes myb/genética , Humanos , Imidazóis/farmacologia , Imidazóis/uso terapêutico , Oxazepinas/farmacologia , Oxazepinas/uso terapêutico , Doenças das Plantas/parasitologia , Doenças das Plantas/terapia , Raízes de Plantas/citologia , Raízes de Plantas/metabolismo , Raízes de Plantas/parasitologia , Plasmodioforídeos/crescimento & desenvolvimento , Alinhamento de Sequência , Esporos de Protozoários/efeitos dos fármacos , Esporos de Protozoários/genética , Transcriptoma/efeitos dos fármacos , Quinases raf/genética
14.
Hemoglobin ; 42(2): 103-107, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30200835

RESUMO

The hemoglobinopathies, as ß-thalassemia (ß-thal) and sickle cell disease, are the most common hereditary hemolytic anemias. The increase of fetal hemoglobin (Hb F) levels can ameliorate the symptoms of hemoglobinopathies. There are several transcription factors such as MYB and SOX-6, which are involved in the regulation of Hb F. There are not enough studies investigating the association between single nucleotide polymorphisms (SNPs) of the SOX-6 and MYB genes and the variation of Hb F levels in patients affected by sickle cell disease and ß-thal. We therefore decided to analyze the role of four missense variants of MYB and SOX-6 genes in the regulation of Hb F levels. In order to do so, we examinated 30 Sicilian patients affected by sickle cell disease and ß-thal, to understand if these variants could also have an influence in our populations. Comparing two groups of patients with low and high levels of Hb F, we found no significant differences in the genetic distribution and allelic frequency of MYB and SOX-6 gene polymorphisms. We also created and compared a 'high producer' and 'low producer' genotype with different genes achieving the same result of no significant difference. Our results may be due either to the fact that the association between these genes and the regulation of Hb F levels are influenced by environmental history and population genetics, or to the small number of samples being analyzed.


Assuntos
Anemia Falciforme/genética , Hemoglobina Fetal/genética , Genes myb/genética , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição SOXD/genética , Talassemia beta/genética , Frequência do Gene , Hemoglobinopatias/genética , Humanos , Sicília/epidemiologia
15.
Genes Genomics ; 40(1): 49-61, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29892898

RESUMO

Flavonoids are a group of metabolites in Ginkgo biloba thought to provide health benefits. R2R3-MYB transcription factors (TFs) play key roles in the transcriptional regulation of the flavonoid biosynthesis in plants. In this study, an R2R3-MYB transcription factor gene, GbMYBFL, was isolated from G. biloba and characterized. Results of bioinformatic analysis indicated that GbMYBFL is more closely related to the R2R3-MYB involved in flavonoid biosynthesis and displayed high similarity to MYB from other plants. The genmomic sequence of GbMYBFL had three exons and two introns, with its upstream sequence containing cis-acting regulatory elements Myb binding site, Myc recognition sites, and light, SA, MeJA responsive elements. Subcellular localization analysis indicates that GbMYBFL was located in the nucleus. Quantitative real-time PCR revealed that GbMYBFL was expressed in leaves, stems, roots, young fruits, male flower and female flower, and the level of transcription in male flower and leaves were higher than that in female flower, stems, roots, and young fruits. During G. biloba leaf growth, the transcription of GbMYBFL is positively correlated with the flavonoid content, suggesting that the GbMYBFL is involved in the flavonoid biosynthesis. Overexpression of GbMYBFL under the control of the CaMV35S promoter in Ginkgo callus notably enhanced the accumulation of flavonoids and anthocyanin compared with non-transformed callus. This finding suggested that GbMYBFL positively related to flavonoid biosynthesis, and the overexpression of GbMYBFL was sufficient to induce flavonoids and anthocyanin accumulation.


Assuntos
Genes myb/genética , Ginkgo biloba/genética , Sequência de Aminoácidos/genética , Antocianinas/biossíntese , Sequência de Bases/genética , Flavonoides/biossíntese , Flavonoides/genética , Flores/metabolismo , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Genes de Plantas/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Raízes de Plantas/metabolismo , Regiões Promotoras Genéticas/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transcriptoma
16.
Artigo em Inglês | MEDLINE | ID: mdl-29860170

RESUMO

G-quadruplex DNAs are involved in a number of key biological processes, including gene expression, transcription, and apoptosis. The c-myb oncogene contains a number of GGA repeats in its promoter which forms G-quadruplex, thus it could be used as a target in cancer therapeutics. Several in-vitro studies have used Circular Dichroism (CD) spectroscopy or electrospray ionization mass spectrometry (ESI-MS) to demonstrate formation and stability of G-quadruplex DNA structure in the promoter region of human c-myb oncogene. The factors affecting the c-myb G-quadruplex structures were investigated, such as cations (i.e. K+, NH4+ and Na+) and co-solutes (methanol and polyethylene glycol). The results indicated that the presence of cations and co-solutes could change the G-quadruplex structural population and promote its thermodynamic stabilization as indicated by CD melting curves. It indicated that the co-solutes preferentially stabilize the c-myb G-quadruplex structure containing both homo- and hetero-stacking. In addition, protopine was demonstrated as a binder of c-myb G-quadruplex as screened from a library of natural alkaloids using ESI-MS method. CD spectra showed that it could selectively stabilize the c-myb G-quadruplex structure compared to other six G-quadruplexes from tumor-related G-rich sequences and the duplex DNAs (both long and short-chain ones). The binding of protopine could induce the change in the G-quadruplex structural populations. Therefore, protopine with its high binding specificity could be considered as a precursor for the design of drugs to target and regulate c-myb oncogene transcription.


Assuntos
DNA/metabolismo , Quadruplex G , Genes myb , Espectrometria de Massas por Ionização por Electrospray/métodos , Alcaloides/química , Alcaloides/metabolismo , Dicroísmo Circular , Humanos , Regiões Promotoras Genéticas/genética , Temperatura de Transição
17.
PLoS One ; 13(6): e0199192, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29927971

RESUMO

The MYB transcription factor superfamily is one of the largest superfamilies modulating various biological processes in plants. Over the past few decades, many MYB superfamily genes have been identified and characterized in some plant species. However, genes belonging to the MYB superfamily in peach (Prunus persica) have not been comprehensively identified and characterized although the genome sequences of peach were released several years ago. In total, this study yielded a set of 256 MYB superfamily genes that was divided into five subfamilies: the R2R3-MYB (2R-MYB), R1R2R3-MYB (3R-MYB), MYB-related (1R-MYB), 4R-MYB, and Atypical-MYB subfamilies. These subfamilies contained 128, 4, 109, 1, and 14 members, respectively. The 128 R2R3-MYB subfamily genes in peach were further clustered into 35 groups, and the 109 MYB-related subfamily genes were further clustered into 6 groups: the CCA1-like, CPC-like, TBP-like, I-box-binding-like, R-R-type, and Peach-specific groups. The motif compositions and exon/intron structures within each group within the R2R3-MYB or MYB-related subfamily in peach were highly conserved. The logo sequences of the R2 and R3 repeats of R2R3-MYB subfamily members were highly conserved with those in these repeats of several other plant species. Except for 48 novel peach-specific MYB genes, the remaining 208 out of 256 MYB genes in peach were conserved with the corresponding 198 MYB genes in A. thaliana. Additionally, the 256 MYB genes unevenly distributed on chromosomes 1 to 8 of the peach genome. Eighty-one orthologous pairs of peach/A. thaliana MYB genes were identified among 256 MYB genes in peach and 198 MYB genes in A. thaliana in this study. In addition, 146 pairs of paralogous MYB genes were identified on the eight chromosomes of peach. The expression levels of some of the 51 MYB genes selected for qRT-PCR analysis decreased or increased with red-fleshed fruit development, while the expression patterns of some genes followed no clear rules over the five developmental stages of fruits. This study laid the foundation for further functional analysis of MYB superfamily genes in peach and enriched the knowledge of MYB superfamily genes in plant species.


Assuntos
Regulação da Expressão Gênica de Plantas , Genes myb , Genoma de Planta , Proteínas de Plantas/genética , Prunus persica/genética , Família Multigênica
18.
Leukemia ; 32(12): 2590-2603, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29795241

RESUMO

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare skin-tropic hematological malignancy of uncertain pathogenesis and poor prognosis. We examined 118 BPDCN cases for cytomorphology, MYC locus rearrangement, and MYC expression. Sixty-two (53%) and 41 (35%) cases showed the classic and immunoblastoid cytomorphology, respectively. Forty-one (38%) MYC+BPDCN (positive for rearrangement and expression) and 59 (54%) MYC-BPDCN (both negative) cases were identified. Immunoblastoid cytomorphology was significantly associated with MYC+BPDCN. All examined MYC+BPDCNs were negative for MYB/MYBL1 rearrangement (0/36). Clinically, MYC+BPDCN showed older onset, poorer outcome, and localized skin tumors more commonly than MYC-BPDCN. MYC was demonstrated by expression profiling as one of the clearest discriminators between CAL-1 (MYC+BPDCN) and PMDC05 (MYC-BPDCN) cell lines, and its shRNA knockdown suppressed CAL-1 viability. Inhibitors for bromodomain and extra-terminal protein (BETis), and aurora kinases (AKis) inhibited CAL-1 growth more effectively than PMDC05. We further showed that a BCL2 inhibitor was effective in both CAL-1 and PMDC05, indicating that this inhibitor can be used to treat MYC-BPDCN, to which BETis and AKis are probably less effective. Our data will provide a rationale for the development of new treatment strategies for patients with BPDCN, in accordance with precision medicine.


Assuntos
Células Dendríticas/patologia , Rearranjo Gênico/genética , Neoplasias Hematológicas/genética , Neoplasias Cutâneas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Sobrevivência Celular/genética , Criança , Pré-Escolar , Feminino , Genes myb/genética , Genes myc/genética , Neoplasias Hematológicas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas/genética , RNA Interferente Pequeno , Neoplasias Cutâneas/patologia , Adulto Jovem
19.
J Immunol Methods ; 457: 66-72, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29630967

RESUMO

Allogeneic bone marrow (BM) transplantation enables the in vivo functional assessment of hematopoietic cells. As pre-conditioning, ionizing radiation is commonly applied to induce BM depletion, however, it exerts adverse effects on the animal and can limit experimental outcome. Here, we provide an alternative method that harnesses conditional gene deletion to ablate c-myb and thereby deplete BM cells, hence allowing BM substitution without other pre-conditioning. The protocol results in a high level of blood chimerism after allogeneic BM transplantation, whereas immune cells in peripheral tissues such as resident macrophages are not replaced. Further, mice featuring a low chimerism after initial transplantation can undergo a second induction cycle for efficient deletion of residual BM cells without the necessity to re-apply donor cells. In summary, we present an effective c-myb-dependent genetic technique to generate BM chimeras in the absence of irradiation or other methods for pre-conditioning.


Assuntos
Transplante de Medula Óssea/métodos , Deleção de Genes , Genes myb/genética , Transplante de Células-Tronco Hematopoéticas/métodos , Quimeras de Transplante , Animais , Feminino , Tolerância Imunológica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Poli I-C/administração & dosagem , Radiação Ionizante , Condicionamento Pré-Transplante , Transplante Homólogo
20.
Future Oncol ; 14(16): 1579-1589, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29517281

RESUMO

AIM: In this study, we investigated the role of Y-box binding protein-1 (YB-1), c-Myb and miR-155 in human laryngeal squamous cell carcinoma (LSCC) progression. MATERIALS & METHODS: Quantitative real-time PCR, western blot, MTT and Transwell were conducted to determine the expression and function of YB-1/miR-155 pathway. Univariate and multivariate analyses were used to determine the prognostic factors. RESULTS: Expression of YB-1, c-Myb and miR-155 was higher in LSCC tissues. YB-1 promoted proliferation, invasiveness and migration of Hep-2 cells in vitro. Patients with higher YB-1 correlated with advanced T stage, poor differentiation and cervical metastasis. LSCC patients with high YB-1 expression showed poor overall survival. CONCLUSION: YB-1 promotes LSCC progression by increasing miR-155 levels via c-Myb and acts as a prognostic factor.


Assuntos
Carcinoma de Células Escamosas/patologia , Genes myb/genética , Neoplasias Laríngeas/patologia , MicroRNAs/genética , Proteína 1 de Ligação a Y-Box/genética , Idoso , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteína 1 de Ligação a Y-Box/metabolismo
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