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1.
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
2.
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
3.
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
4.
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
5.
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
6.
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
7.
Int J Biol Macromol ; 107(Pt B): 1474-1479, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28987798

RESUMO

Our bioinformatics research shows that there are four G-rich sequences (S1-S4) in the upstream region of the transcription start site of c-Myb gene, and we have proved that these sequences have the ability to form G-quadruplex structures. This work mainly focuses on G-quadruplex function, recognition and transcription regulation in c-Myb gene, revealing a novel regulatory element in c-Myb proximal promoter region, and its transcription regulation by G-quadruplex binder. The research has identified that the enhancer effect in c-Myb transcription was primarily affected by the G-quadruplex formed by S1 sequence, and the up-regulation effect may due to the removal of repressive progress of MZF-1 by stabilizing G-quadruplex. Attentions were being paid to the development of G-quadruplex binders for selective recognition, and topotecan was found to have high binding affinity in vitro and could effectively affect the c-Myb transcription activities in cells. The regulation of G-quadruplex with binders in transcriptional, translational levels by Q-RT-PCR and western blot was in expectation of providing a strategy for gene expression modulation. In conclusion, our study revealed a G-quadruplex structure in c-Myb proximal promoter region, which was of great importance in the regulation of c-Myb function.


Assuntos
Quadruplex G , Regulação da Expressão Gênica/efeitos dos fármacos , Genes myb , Topotecan/farmacologia , Transcrição Genética/efeitos dos fármacos , Sequência de Bases , Elementos Facilitadores Genéticos/genética , Genes Reporter , Humanos , Luciferases/metabolismo , Células MCF-7 , Biossíntese de Proteínas/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia , Topotecan/química
8.
Plant Cell Physiol ; 58(10): 1777-1788, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29016897

RESUMO

MYB transcription factors are widespread in plants and play key roles in plant development. Although MYB transcription factors have been thoroughly characterized in many plants, genome-wide analysis of the MYB gene family has not yet been undertaken in Brachypodium distachyon. In this study, 122 BdMYB transcription factors were identified, comprising 85 MYB-R2R3, 34 MYB-related and three MYB-R1R2R3. Phylogenetic analysis showed that BdMYBs, OsMYBs and AtMYBs with similar functions were clustered in the same subgroup, and the phylogenetic relationships of BdMYB transcription factors were supported by highly conserved motifs and gene structures. Two cis-elements were found in the promoters of BdMYB genes. One is related to plant growth/development, the other is related to stress responses. Gene Ontology (GO) analysis indicated that most of the BdMYB genes are involved in various biological processes. The chromosome distribution pattern strongly indicated that genome-wide tandem and segment duplication mainly contributed to the expansion of the BdMYB gene family. Synteny analysis showed that 56, 58 and 61 BdMYB genes were orthologous to rice, maize and sorghum, respectively. We further demonstrated that BdMYB genes have evolved under strong purifying selection. The expression profiles indicated that most BdMYB genes might participate in floral development and respond to abiotic stresses. Additionally, 338 pairs of proteins were predicted to interact by constructing the interaction network. This work laid the foundation and provided clues for understanding the biological functions of these transcription factors.


Assuntos
Brachypodium/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genes myb , Genoma de Planta , Motivos de Aminoácidos , Cromossomos de Plantas/genética , Sequência Conservada/genética , Duplicação Gênica , Ontologia Genética , Genes de Plantas , Anotação de Sequência Molecular , Filogenia , Mapeamento Físico do Cromossomo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regiões Promotoras Genéticas , Mapas de Interação de Proteínas , Estresse Fisiológico/genética , Sintenia/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
10.
J Exp Bot ; 68(15): 4153-4169, 2017 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-28922762

RESUMO

Plant phloem-based defence (PBD) against phloem-feeding insects is characteristic of the sieve occlusion by phloem lectins and ß-1,3-glucan callose, both of which are produced under regulation by ethylene and MYB transcription factors. Wheat PBD requires ß-1,3-glucan synthase-like proteins GSL2, GSL10, and GSL12, and may also require insect-resistant mannose-binding lectins Hfr-1 and Wci-1, which can accumulate in the phloem upon aphid feeding. This study elucidates whether any of the 73 MYB genes identified previously in the common wheat Triticum aestivum genome plays a role in wheat PBD activation with regard to the GSLs and lectins. Wheat MYB genes TaMYB19, TaMYB29, and TaMYB44 are highly activated in response to infestation of English grain aphid, and their silencing facilitates aphid feeding on wheat phloem and represses wheat PBD responses. Repressed PBD is shown to decrease aphid-induced callose deposition in wheat leaf epidermis and decrease aphid-induced expression of genes GSL2, GSL10, GSL12, Hfr-1, and Wci-1 in wheat leaf tissues. Based on single gene silencing effects, TaMYB19, TaMYB29, and TaMYB44 contribute 55-82% of PBD responses. However, the contributions of TaMYB genes to PBD are eliminated by ethylene signalling inhibitors, while simultaneous silencing of the three TaMYB genes cancels the tested PBD responses. Therefore, TaMYB19, TaMYB29, and TaMYB44 are co-regulators of wheat PBD and execute this function through crosstalk with the ethylene signalling pathway.


Assuntos
Antibiose , Afídeos/fisiologia , Regulação da Expressão Gênica de Plantas , Genes myb/genética , Herbivoria , Proteínas de Plantas/genética , Triticum/fisiologia , Animais , Afídeos/crescimento & desenvolvimento , Ninfa/crescimento & desenvolvimento , Ninfa/fisiologia , Floema/metabolismo , Proteínas de Plantas/metabolismo , Triticum/genética
11.
BMC Plant Biol ; 17(1): 142, 2017 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-28830364

RESUMO

BACKGROUND: MYB transcription factors (TFs) are one of the largest families of TFs in higher plants and are involved in diverse biological, functional, and structural processes. Previously, very few functional validation studies on R2R3 MYB have been conducted in cotton in response to abiotic stresses. In the current study, GaMYB85, a cotton R2R3 MYB TF, was ectopically expressed in Arabidopsis thaliana (Col-0) and was functionally characterized by overexpression in transgenic plants. RESULTS: The in-silico analysis of GaMYB85 shows the presence of a SANT domain with a conserved R2R3 MYB imperfect repeat. The GaMYB85 protein has a 257-amino acid sequence, a molecular weight of 24.91 kD, and an isoelectric point of 5.58. Arabidopsis plants overexpressing GaMYB85 exhibited a higher seed germination rate in response to mannitol and salt stress, and higher drought avoidance efficiency than wild-type plants upon water deprivation. These plants had notably higher levels of free proline and chlorophyll with subsequent lower water loss rates and higher relative water content. Germination of GaMYB85 transgenics was more sensitive to abscisic acid (ABA) and extremely liable to ABA-induced inhibition of primary root elongation. Moreover, when subjected to treatment with different concentrations of ABA, transgenic plants with ectopically expressed GaMYB85 showed reduced stomatal density, with greater stomatal size and lower stomatal opening rates than those in wild-type plants. Ectopic expression of GaMYB85 led to enhanced transcript levels of stress-related marker genes such as RD22, ADH1, RD29A, P5CS, and ABI5. CONCLUSIONS: Our results indicate previously unknown roles of GaMYB85, showing that it confers good drought, salt, and freezing tolerance, most probably via an ABA-induced pathway. These findings can potentially be exploited to develop improved abiotic stress tolerance in cotton plants.


Assuntos
Aclimatação , Arabidopsis/fisiologia , Secas , Genes myb/genética , Proteínas de Plantas/genética , Sequência de Aminoácidos , Arabidopsis/genética , Gossypium/genética , Gossypium/fisiologia , Filogenia , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/fisiologia , Análise de Sequência de DNA
12.
Histopathology ; 71(5): 823-834, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28594149

RESUMO

AIMS: Adenoid cystic carcinoma (AdCC) is one of the most common salivary gland malignancies and the long-term prognosis is poor. In this study, we examined alterations of AdCC-associated genes, MYB, MYBL1, MYBL2 and NFIB, and their target molecules, including MYC. The results were correlated to clinicopathological profile of the patients. METHODS AND RESULTS: Using paraffin tumour sections from 33 cases of salivary gland AdCC, we performed a detailed fluorescence in-situ hybridization (FISH) analysis for gene splits and fusions of MYB, MYBL1, MYBL2 and NFIB. We found that 29 of 33 (88%) AdCC cases showed gene splits in either MYB, MYBL1 or NFIB. None of the cases showed an MYBL2 gene alteration. AdCCs were divided genetically into six gene groups, MYB-NFIB (n = 16), MYB-X (n = 4), MYBL1-NFIB (n = 2), MYBL1-X (n = 1), NFIB-X (n = 6) and gene-split-negative (n = 4). AdCC patients showing the MYB or MYBL1 gene splits were associated with microscopically positive surgical margins (P = 0.0148) and overexpression of MYC (P = 0.0164). MYC expression was detected in both ductal and myoepithelial tumour cells, and MYC overexpression was associated with shorter disease-free survival of the patients (P = 0.0268). CONCLUSIONS: The present study suggests that (1) nearly 90% of AdCCs may have gene alterations of either MYB, MYBL1 or NFIB, suggesting the diagnostic utility of the FISH assay, (2) MYB or MYBL1 gene splits may be associated with local aggressiveness of the tumours and overexpression of MYC, which is one of the oncogenic MYB/MYBL1 targets and (3) MYC overexpression may be a risk factor for disease-free survival in AdCC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Adenoide Cístico/genética , Neoplasias das Glândulas Salivares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Carcinoma Adenoide Cístico/mortalidade , Carcinoma Adenoide Cístico/patologia , Proteínas de Ciclo Celular/genética , Feminino , Genes myb , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Fatores de Transcrição NFI/genética , Proteínas Oncogênicas v-myb/genética , Modelos de Riscos Proporcionais , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-myc/genética , Neoplasias das Glândulas Salivares/mortalidade , Neoplasias das Glândulas Salivares/patologia , Transativadores/genética , Translocação Genética
13.
Nucleic Acids Res ; 45(13): 7681-7696, 2017 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-28472346

RESUMO

The transcription factor c-Myb is involved in early differentiation and proliferation of haematopoietic cells, where it operates as a regulator of self-renewal and multi-lineage differentiation. Deregulated c-Myb plays critical roles in leukaemias and other human cancers. Due to its role as a master regulator, we hypothesized it might function as a pioneer transcription factor. Our approach to test this was to analyse a mutant of c-Myb, D152V, previously reported to cause haematopoietic defects in mice by an unknown mechanism. Our transcriptome data from K562 cells indicates that this mutation specifically affects c-Myb's ability to regulate genes involved in differentiation, causing failure in c-Myb's ability to block differentiation. Furthermore, we see a major effect of this mutation in assays where chromatin opening is involved. We show that each repeat in the minimal DNA-binding domain of c-Myb binds to histones and that D152V disrupts histone binding of the third repeat. ATAC-seq data indicates this mutation impairs the ability of c-Myb to cause chromatin opening at specific sites. Taken together, our findings support that c-Myb acts as a pioneer factor and show that D152V impairs this function. The D152V mutant is the first mutant of a transcription factor specifically destroying pioneer factor function.


Assuntos
Diferenciação Celular/genética , Genes myb , Histonas/metabolismo , Mutação , Proteínas Proto-Oncogênicas c-myb/genética , Proteínas Proto-Oncogênicas c-myb/metabolismo , Substituição de Aminoácidos , Animais , Cromatina/genética , Cromatina/metabolismo , Eritropoese/genética , Técnicas de Silenciamento de Genes , Humanos , Células K562 , Camundongos , Modelos Moleculares , Proteínas Mutantes/química , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Ligação Proteica , Domínios Proteicos , Proteínas Proto-Oncogênicas c-myb/química
16.
New Phytol ; 214(4): 1614-1630, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28332702

RESUMO

In the hyperaccumulator Arabidopsis halleri, the zinc (Zn) vacuolar transporter MTP1 is a key component of hypertolerance. Because protein sequences and functions are highly conserved between A. halleri and Arabidopsis thaliana, Zn tolerance in A. halleri may reflect the constitutively higher MTP1 expression compared with A. thaliana, based on copy number expansion and different cis regulation. Three MTP1 promoters were characterized in A. halleri ecotype I16. The comparison with the A. thaliana MTP1 promoter revealed different expression profiles correlated with specific cis-acting regulatory elements. The MTP1 5' untranslated region, highly conserved among A. thaliana, Arabidopsis lyrata and A. halleri, contains a dimer of MYB-binding motifs in the A. halleri promoters absent in the A. thaliana and A. lyrata sequences. Site-directed mutagenesis of these motifs revealed their role for expression in trichomes. A. thaliana mtp1 transgenic lines expressing AtMTP1 controlled by the native A. halleri promoter were more Zn-tolerant than lines carrying mutations on MYB-binding motifs. Differences in Zn tolerance were associated with different distribution of Zn among plant organs and in trichomes. The different cis-acting elements in the MTP1 promoters of A. halleri, particularly the MYB-binding sites, are probably involved in the evolution of Zn tolerance.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Transporte de Cátions/genética , Metais/metabolismo , Regiões Promotoras Genéticas , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Sítios de Ligação , Evolução Biológica , Brassicaceae/genética , Proteínas de Transporte de Cátions/metabolismo , Códon de Iniciação , Regulação da Expressão Gênica de Plantas , Genes myb , Itália , Mutagênese Sítio-Dirigida , Plantas Geneticamente Modificadas , Tricomas/genética , Zinco/metabolismo
17.
Leukemia ; 31(10): 2057-2064, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28260788

RESUMO

Oncogenic driver mutations are those that provide a proliferative or survival advantage to neoplastic cells, resulting in clonal selection. Although most cancer-causing mutations have been detected in the protein-coding regions of the cancer genome; driver mutations have recently also been discovered within noncoding genomic sequences. Thus, a current challenge is to gain precise understanding of how these unique genomic elements function in cancer pathogenesis, while clarifying mechanisms of gene regulation and identifying new targets for therapeutic intervention. Here we report a C-to-T single nucleotide transition that occurs as a somatic mutation in noncoding sequences 4 kb upstream of the transcriptional start site of the LMO1 oncogene in primary samples from patients with T-cell acute lymphoblastic leukaemia. This single nucleotide alteration conforms to an APOBEC-like cytidine deaminase mutational signature, and generates a new binding site for the MYB transcription factor, leading to the formation of an aberrant transcriptional enhancer complex that drives high levels of expression of the LMO1 oncogene. Since APOBEC-signature mutations are common in a broad spectrum of human cancers, we suggest that noncoding nucleotide transitions such as the one described here may activate potent oncogenic enhancers not only in T-lymphoid cells but in other cell lineages as well.


Assuntos
Desaminases APOBEC/metabolismo , Proteínas de Ligação a DNA/biossíntese , Elementos Facilitadores Genéticos/genética , Regulação Leucêmica da Expressão Gênica/genética , Proteínas com Domínio LIM/biossíntese , Proteínas de Neoplasias/biossíntese , Mutação Puntual , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Fatores de Transcrição/biossíntese , Transcriptoma , Regiões 5' não Traduzidas/genética , Sequência de Bases , Sítios de Ligação , Linhagem Celular Tumoral , Criança , Imunoprecipitação da Cromatina , DNA de Neoplasias/genética , Proteínas de Ligação a DNA/genética , Genes myb , Humanos , Células Jurkat , Proteínas com Domínio LIM/genética , Proteínas de Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Proteínas Proto-Oncogênicas c-myb/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-myb/genética , Proteínas Proto-Oncogênicas c-myb/metabolismo , Interferência de RNA , RNA Interferente Pequeno/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
18.
PLoS One ; 12(2): e0172695, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28234982

RESUMO

Lignin and polyphenols are important cellular components biosynthesized through phenylpropanoid pathway. Phenylpropanoid pathway in plants is regulated by some important transcription factors including R2R3 MYB transcription factors. In this study, we report the cloning and functional characterization of a banana R2R3-MYB transcription factor (MusaMYB31) by overexpression in transgenic banana plants and evaluated its potential role in regulating biosynthesis of lignin and polyphenols. Sequence analysis of MusaMYB31 indicated its clustering with members of subgroup 4 (Sg4) of R2R3MYB family which are well known for their role as repressors of lignin biosynthesis. Expression analysis indicated higher expression of MusaMYB31 in corm and root tissue, known for presence of highly lignified tissue than other organs of banana. Overexpression of MusaMYB31 in banana cultivar Rasthali was carried out and four transgenic lines were confirmed by GUS histochemical staining, PCR analysis and Southern blot. Histological and biochemical analysis suggested reduction of cell wall lignin in vascular elements of banana. Transgenic lines showed alteration in transcript levels of general phenylpropanoid pathway genes including lignin biosynthesis pathway genes. Reduction of total polyphenols content in transgenic lines was in line with the observation related to repression of general phenylpropanoid pathway genes. This study suggested the potential role of MusaMYB31 as repressor of lignin and polyphenols biosynthesis in banana.


Assuntos
Parede Celular/genética , Regulação da Expressão Gênica de Plantas , Genes myb , Musa/genética , Proteínas de Plantas/genética , Fatores de Transcrição/genética , Sequência de Aminoácidos , Parede Celular/metabolismo , Parede Celular/ultraestrutura , Lignina/biossíntese , Musa/metabolismo , Fenilpropionatos/metabolismo , Filogenia , Folhas de Planta/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Polifenóis/biossíntese , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Fatores de Transcrição/metabolismo
19.
Stem Cell Reports ; 8(2): 334-345, 2017 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-28111278

RESUMO

Tissue-resident macrophages, such as microglia, Kupffer cells, and Langerhans cells, derive from Myb-independent yolk sac (YS) progenitors generated before the emergence of hematopoietic stem cells (HSCs). Myb-independent YS-derived resident macrophages self-renew locally, independently of circulating monocytes and HSCs. In contrast, adult blood monocytes, as well as infiltrating, gut, and dermal macrophages, derive from Myb-dependent HSCs. These findings are derived from the mouse, using gene knockouts and lineage tracing, but their applicability to human development has not been formally demonstrated. Here, we use human induced pluripotent stem cells (iPSCs) as a tool to model human hematopoietic development. By using a CRISPR-Cas9 knockout strategy, we show that human iPSC-derived monocytes/macrophages develop in an MYB-independent, RUNX1-, and SPI1 (PU.1)-dependent fashion. This result makes human iPSC-derived macrophages developmentally related to and a good model for MYB-independent tissue-resident macrophages, such as alveolar and kidney macrophages, microglia, Kupffer cells, and Langerhans cells.


Assuntos
Diferenciação Celular , Genes myb , Células-Tronco Pluripotentes Induzidas/citologia , Macrófagos/metabolismo , Biomarcadores , Linhagem Celular , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Corpos Embrioides/citologia , Corpos Embrioides/metabolismo , Eritrócitos/citologia , Eritrócitos/metabolismo , Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Inativação de Genes , Granulócitos/citologia , Granulócitos/metabolismo , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Humanos , Macrófagos/citologia , Monócitos/metabolismo , Monócitos/patologia , Especificidade de Órgãos , Fenótipo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Transativadores/genética , Transativadores/metabolismo
20.
J Cutan Pathol ; 44(2): 201-209, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27859477

RESUMO

Adenoid cystic carcinoma (ACC) is a relatively rare slow-growing and often-aggressive epithelial-myoepithelial neoplasm that arises in multiple organs including the skin. The t(6;9) (q22-23;p23-24) translocation, resulting in a MYB-NFIB gene fusion has been found in ACCs from the salivary glands and other organs. Recently, MYB aberrations occurring in a subset (40%) of primary cutaneous ACC (PCACC) examples was described. Herein, we report three additional cases of PCACC harboring MYB aberrations. The tumors presented in three males aged 43, 81 and 55 years old and affected the extremities in the first two patients and the scalp in the third one. None of the patients had history of prior or concurrent ACC elsewhere. Lesions exhibited the classic ACC morphology of nests of basaloid cells arranged in cribriform and adenoid patterns. Sentinel lymph node biopsy was performed in two cases with one case showing lymph node positivity. Fluorescence in situ hybridization with break-apart probes for MYB and NFIB loci revealed that two cases showed MYB rearrangements while one case showed loss of one MYB signal. None of the cases showed NFIB rearrangements. We contribute with three additional cases of PCACC exhibiting MYB aberrations, the apparent driving genetic abnormality in these tumors.


Assuntos
Carcinoma Adenoide Cístico/genética , Carcinoma Adenoide Cístico/patologia , Genes myb/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Adulto , Idoso de 80 Anos ou mais , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade
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