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1.
Nature ; 603(7902): 667-671, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35296862

RESUMEN

Most social species self-organize into dominance hierarchies1,2, which decreases aggression and conserves energy3,4, but it is not clear how individuals know their social rank. We have only begun to learn how the brain represents social rank5-9 and guides behaviour on the basis of this representation. The medial prefrontal cortex (mPFC) is involved in social dominance in rodents7,8 and humans10,11. Yet, precisely how the mPFC encodes relative social rank and which circuits mediate this computation is not known. We developed a social competition assay in which mice compete for rewards, as well as a computer vision tool (AlphaTracker) to track multiple, unmarked animals. A hidden Markov model combined with generalized linear models was able to decode social competition behaviour from mPFC ensemble activity. Population dynamics in the mPFC predicted social rank and competitive success. Finally, we demonstrate that mPFC cells that project to the lateral hypothalamus promote dominance behaviour during reward competition. Thus, we reveal a cortico-hypothalamic circuit by which the mPFC exerts top-down modulation of social dominance.


Asunto(s)
Hipotálamo , Corteza Prefrontal , Animales , Área Hipotalámica Lateral , Ratones , Recompensa , Conducta Social
2.
Mol Biol Evol ; 41(9)2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39213378

RESUMEN

Polyploidization drives regulatory and phenotypic innovation. How the merger of different genomes contributes to polyploid development is a fundamental issue in evolutionary developmental biology and breeding research. Clarifying this issue is challenging because of genome complexity and the difficulty in tracking stochastic subgenome divergence during development. Recent single-cell sequencing techniques enabled probing subgenome-divergent regulation in the context of cellular differentiation. However, analyzing single-cell data suffers from high error rates due to high dimensionality, noise, and sparsity, and the errors stack up in polyploid analysis due to the increased dimensionality of comparisons between subgenomes of each cell, hindering deeper mechanistic understandings. In this study, we develop a quantitative computational framework, called "pseudo-genome divergence quantification" (pgDQ), for quantifying and tracking subgenome divergence directly at the cellular level. Further comparing with cellular differentiation trajectories derived from single-cell RNA sequencing data allows for an examination of the relationship between subgenome divergence and the progression of development. pgDQ produces robust results and is insensitive to data dropout and noise, avoiding high error rates due to multiple comparisons of genes, cells, and subgenomes. A statistical diagnostic approach is proposed to identify genes that are central to subgenome divergence during development, which facilitates the integration of different data modalities, enabling the identification of factors and pathways that mediate subgenome-divergent activity during development. Case studies have demonstrated that applying pgDQ to single-cell and bulk tissue transcriptomic data promotes a systematic and deeper understanding of how dynamic subgenome divergence contributes to developmental trajectories in polyploid evolution.


Asunto(s)
Poliploidía , Análisis de la Célula Individual , Análisis de la Célula Individual/métodos , Animales , Biología Computacional/métodos
3.
Plant Cell ; 34(1): 579-596, 2022 01 20.
Artículo en Inglés | MEDLINE | ID: mdl-34735009

RESUMEN

The self-incompatibility (SI) system with the broadest taxonomic distribution in angiosperms is based on multiple S-locus F-box genes (SLFs) tightly linked to an S-RNase termed type-1. Multiple SLFs collaborate to detoxify nonself S-RNases while being unable to detoxify self S-RNases. However, it is unclear how such a system evolved, because in an ancestral system with a single SLF, many nonself S-RNases would not be detoxified, giving low cross-fertilization rates. In addition, how the system has been maintained in the face of whole-genome duplications (WGDs) or lost in other lineages remains unclear. Here we show that SLFs from a broad range of species can detoxify S-RNases from Petunia with a high detoxification probability, suggestive of an ancestral feature enabling cross-fertilization and subsequently modified as additional SLFs evolved. We further show, based on its genomic signatures, that type-1 was likely maintained in many lineages, despite WGD, through deletion of duplicate S-loci. In other lineages, SI was lost either through S-locus deletions or by retaining duplications. Two deletion lineages regained SI through type-2 (Brassicaceae) or type-4 (Primulaceae), and one duplication lineage through type-3 (Papaveraceae) mechanisms. Thus, our results reveal a highly dynamic process behind the origin, maintenance, loss, and regain of SI.


Asunto(s)
Evolución Biológica , Células Germinativas de las Plantas/fisiología , Magnoliopsida/fisiología , Autoincompatibilidad en las Plantas con Flores , Autoincompatibilidad en las Plantas con Flores/genética
4.
Mol Biol Evol ; 40(4)2023 04 04.
Artículo en Inglés | MEDLINE | ID: mdl-37014787

RESUMEN

The genus Antirrhinum has been used as a model to study self-incompatibility extensively. The multi-allelic S-locus, carrying a pistil S-RNase and dozens of S-locus F-box (SLF) genes, underlies the genetic control of self-incompatibility (SI) in Antirrhinum hispanicum. However, there have been limited studies on the genomic organization of the S-locus supergene due to a lack of high-quality genomic data. Here, we present the chromosome-level reference and haplotype-resolved genome assemblies of a self-incompatible A. hispanicum line, AhS7S8. For the first time, 2 complete A. hispanicum S-haplotypes spanning ∼1.2 Mb and containing a total of 32 SLFs were reconstructed, whereas most of the SLFs derived from retroelement-mediated proximal or tandem duplication ∼122 Mya. Back then, the S-RNase gene and incipient SLFs came into linkage to form the pro-type of type-1 S-locus in the common ancestor of eudicots. Furthermore, we detected a pleiotropic cis-transcription factor (TF) associated with regulating the expression of SLFs, and two miRNAs may control the expression of this TF. Interspecific S-locus and intraspecific S-haplotype comparisons revealed the dynamic nature and polymorphism of the S-locus supergene mediated by continuous gene duplication, segmental translocation or loss, and TE-mediated transposition events. Our data provide an excellent resource for future research on the evolutionary studies of the S-RNase-based self-incompatibility system.


Asunto(s)
Antirrhinum , Antirrhinum/genética , Antirrhinum/metabolismo , Polen/genética , Polen/metabolismo , Evolución Biológica , Ribonucleasas/genética , Ribonucleasas/metabolismo , Proteínas de Plantas/genética
5.
Genome Res ; 31(12): 2276-2289, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34503979

RESUMEN

More than 80% of the wheat genome consists of transposable elements (TEs), which act as major drivers of wheat genome evolution. However, their contributions to the regulatory evolution of wheat adaptations remain largely unclear. Here, we created genome-binding maps for 53 transcription factors (TFs) underlying environmental responses by leveraging DAP-seq in Triticum urartu, together with epigenomic profiles. Most TF binding sites (TFBSs) located distally from genes are embedded in TEs, whose functional relevance is supported by purifying selection and active epigenomic features. About 24% of the non-TE TFBSs share significantly high sequence similarity with TE-embedded TFBSs. These non-TE TFBSs have almost no homologous sequences in non-Triticeae species and are potentially derived from Triticeae-specific TEs. The expansion of TE-derived TFBS linked to wheat-specific gene responses, suggesting TEs are an important driving force for regulatory innovations. Altogether, TEs have been significantly and continuously shaping regulatory networks related to wheat genome evolution and adaptation.

6.
Plant Cell ; 33(4): 865-881, 2021 05 31.
Artículo en Inglés | MEDLINE | ID: mdl-33594406

RESUMEN

Wheat (Triticum aestivum) has a large allohexaploid genome. Subgenome-divergent regulation contributed to genome plasticity and the domestication of polyploid wheat. However, the specificity encoded in the wheat genome determining subgenome-divergent spatio-temporal regulation has been largely unexplored. The considerable size and complexity of the genome are major obstacles to dissecting the regulatory specificity. Here, we compared the epigenomes and transcriptomes from a large set of samples under diverse developmental and environmental conditions. Thousands of distal epigenetic regulatory elements (distal-epiREs) were specifically linked to their target promoters with coordinated epigenomic changes. We revealed that subgenome-divergent activity of homologous regulatory elements is affected by specific epigenetic signatures. Subgenome-divergent epiRE regulation of tissue specificity is associated with dynamic modulation of H3K27me3 mediated by Polycomb complex and demethylases. Furthermore, quantitative epigenomic approaches detected key stress responsive cis- and trans-acting factors validated by DNA Affinity Purification and sequencing, and demonstrated the coordinated interplay between epiRE sequence contexts, epigenetic factors, and transcription factors in regulating subgenome divergent transcriptional responses to external changes. Together, this study provides a wealth of resources for elucidating the epiRE regulomics and subgenome-divergent regulation in hexaploid wheat, and gives new clues for interpreting genetic and epigenetic interplay in regulating the benefits of polyploid wheat.


Asunto(s)
Epigénesis Genética , Secuencias Reguladoras de Ácidos Nucleicos , Estrés Fisiológico/genética , Triticum/genética , Regulación de la Expresión Génica de las Plantas , Genoma de Planta , Histonas/genética , Histonas/metabolismo , Lisina/genética , Lisina/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Triticum/fisiología
7.
J Integr Plant Biol ; 2023 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-37963073

RESUMEN

Self-incompatibility (SI) is an intraspecific reproductive barrier widely present in angiosperms. The SI system with the broadest occurrence in angiosperms is based on an S-RNase linked to a cluster of multiple S-locus F-box (SLF) genes found in the Solanaceae, Plantaginaceae, Rosaceae, and Rutaceae. Recent studies reveal that non-self S-RNase is degraded by the Skip Cullin F-box (SCF)SLF -mediated ubiquitin-proteasome system in a collaborative manner in Petunia, but how self-RNase functions largely remains mysterious. Here, we show that S-RNases form S-RNase condensates (SRCs) in the self-pollen tube cytoplasm through phase separation and the disruption of SRC formation breaks SI in self-incompatible Petunia hybrida. We further find that the pistil SI factors of a small asparagine-rich protein HT-B and thioredoxin h together with a reduced state of the pollen tube all promote the expansion of SRCs, which then sequester several actin-binding proteins, including the actin polymerization factor PhABRACL, the actin polymerization activity of which is reduced by S-RNase in vitro. Meanwhile, we find that S-RNase variants lacking condensation ability fail to recruit PhABRACL and are unable to induce actin foci formation required for pollen tube growth inhibition. Taken together, our results demonstrate that phase separation of S-RNase promotes SI response in P. hybrida, revealing a new mode of S-RNase action.

8.
New Phytol ; 231(3): 1249-1264, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33932295

RESUMEN

In self-incompatible Petunia species, the pistil S-RNase acts as cytotoxin to inhibit self-pollination but is polyubiquitinated by the pollen-specific nonself S-locus F-box (SLF) proteins and subsequently degraded by the ubiquitin-proteasome system (UPS), allowing cross-pollination. However, it remains unclear how S-RNase is restricted by the UPS. Using biochemical analyses, we first show that Petunia hybrida S3 -RNase is largely ubiquitinated by K48-linked polyubiquitin chains at three regions, R I, R II and R III. R I is ubiquitinated in unpollinated, self-pollinated and cross-pollinated pistils, indicating its occurrence before PhS3 -RNase uptake into pollen tubes, whereas R II and R III are exclusively ubiquitinated in cross-pollinated pistils. Transgenic analyses showed that removal of R II ubiquitination resulted in significantly reduced seed sets from cross-pollination and that of R I and R III to a lesser extent, indicating their increased cytotoxicity. Consistent with this, the mutated R II of PhS3 -RNase resulted in a marked reduction of its degradation, whereas that of R I and R III resulted in less reduction. Taken together, we demonstrate that PhS3 -RNase R II functions as a major ubiquitination region for its destruction and R I and R III as minor ones, revealing that its cytotoxicity is primarily restricted by a stepwise UPS mechanism for cross-pollination in P. hybrida.


Asunto(s)
Petunia , Petunia/genética , Petunia/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Polen/metabolismo , Ribonucleasas/genética , Ribonucleasas/metabolismo , Ubiquitinación
9.
BMC Plant Biol ; 20(1): 469, 2020 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-33046012

RESUMEN

BACKGROUND: Ecological environments shape plant architecture and alter the growing season, which provides the basis for wheat genetic improvement. Therefore, understanding the genetic basis of grain yield and yield-related traits in specific ecological environments is important. RESULTS: A structured panel of 96 elite wheat cultivars grown in the High-yield zone of Henan province in China was genotyped using an Illumina iSelect 90 K SNP assay. Selection pressure derived from ecological environments of mountain front and plain region provided the initial impetus for population divergence. This determined the dominant traits in two subpopulations (spike number and spike percentage were dominance in subpopulation 2:1; thousand-kernel weight, grain filling rate (GFR), maturity date (MD), and fertility period (FP) were dominance in subpopulation 2:2), which was also consistent with their inheritance from the donor parents. Genome wide association studies identified 107 significant SNPs for 12 yield-related traits and 10 regions were pleiotropic to multiple traits. Especially, GY was co-located with MD/FP, GFR and HD at QTL-ple5A, QTL-ple7A.1 and QTL-ple7B.1 region. Further selective sweep analysis revealled that regions under selection were around QTLs for these traits. Especially, grain yield (GY) is positively correlated with MD/FP and they were co-located at the VRN-1A locus. Besides, a selective sweep signal was detected at VRN-1B locus which was only significance to MD/FP. CONCLUSIONS: The results indicated that extensive differential in allele frequency driven by ecological selection has shaped plant architecture and growing season during yield improvement. The QTLs for yield and yield components detected in this study probably be selectively applied in molecular breeding.


Asunto(s)
Adaptación Fisiológica/genética , Biota/genética , Grano Comestible/genética , Fitomejoramiento , Triticum/anatomía & histología , Triticum/crecimiento & desarrollo , Triticum/genética , China , Cromosomas de las Plantas , Producción de Cultivos , Regulación de la Expresión Génica de las Plantas , Estudio de Asociación del Genoma Completo , Fenotipo , Estaciones del Año
10.
Theor Appl Genet ; 132(6): 1799-1814, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30824973

RESUMEN

KEY MESSAGE: We isolated a novel allele associated with grain length and grain weight in wheat, TaGL3-5A-G. The TaGL3-5A-G allele frequency is low in wheat, so it has potential for breeding. Selection of large-grain wheat showing big grain sink potential and strong sink activity is becoming an important objective in breeding programs. Here, we cloned a wheat TaGL3-5A gene that was orthologous to rice GL3 and was phylogenetically clustered with both monocot PPKL1 and its expression pattern was similar to grain size change at early and middle stages of seed development. The isolated TaGL3-5A genomic sequence was 10,227 bp long and included 21 exons and 20 introns. Alignment of the TaGL3-5A sequences in Beinong 6 and Yanda 1817 showed a G/A substitution in the 11th exon (position 5946) that would lead to an amino acid change (Met/Ile). Subsequently, a KASP marker was designed based on this SNP. Genotyping of RILs showed that TaGL3-5A was located on the wheat 5AL chromosome and was colocated with a significant grain length QTL in three independent environments and mean value. Association analysis revealed that the TaGL3-5A-G allele was significantly correlated with longer grains and higher thousand-kernel weight. Haplotype association analysis indicated that TaGL3-5A-G could enhance grain traits in combination with TaGS5-3A and TaGW2-6B. The frequency of TaGL3-5A-G was higher in modern cultivars than in landraces but was still low in major Chinese wheat production areas. Additionally, the frequency of the TaGL3-5A-G allele in hexaploid wheat was slightly lower than in Triticum dicoccoides and much lower than in Triticum turgidum. Hence, T. dicoccoides and T. turgidum represent valuable resources for transferring the TaGL3-5A-G allele into common wheat, which should lead to longer grain length.


Asunto(s)
Mapeo Cromosómico/métodos , Cromosomas de las Plantas/genética , Fitomejoramiento , Proteínas de Plantas/genética , Sitios de Carácter Cuantitativo , Semillas/genética , Triticum/genética , Alelos , Evolución Molecular , Ligamiento Genético , Marcadores Genéticos , Fenotipo , Proteínas de Plantas/metabolismo , Semillas/crecimiento & desarrollo , Triticum/crecimiento & desarrollo
11.
BMC Genet ; 20(1): 98, 2019 12 18.
Artículo en Inglés | MEDLINE | ID: mdl-31852431

RESUMEN

BACKGROUND: Grain weight is an important yield component. Selection of advanced lines with heavy grains show high grain sink potentials and strong sink activity, which is an increasingly important objective in wheat breeding programs. Rice OsGS3 has been identified as a major quantitative trait locus for both grain weight and grain size. However, allelic variation of GS3 has not been characterized previously in hexaploid wheat. RESULTS: We cloned 2445, 2393, and 2409 bp sequences of the homologs TaGS3-4A, TaGS3-7A, and TaGS3-7D in wheat 'Changzhi 6406', a cultivar that shows high grain weight. The TaGS3 genes each contained five exons and four introns, and encoded a deduced protein of 170, 169, and 169 amino acids, respectively. Phylogenetic analysis of plant GS3 protein sequences revealed GS3 to be a monocotyledon-specific gene and the GS3 proteins were resolved into three classes. The length of the atypical Gγ domain and the cysteine-rich region was conserved within each class and not conserved between classes. A single-nucleotide polymorphism in the fifth exon (at position 1907) of TaGS3-7A leads to an amino acid change (ALA/THR) and showed different frequencies in two pools of Chinese wheat accessions representing extremes in grain weight. Association analysis indicated that the TaGS3-7A-A allele was associated with higher grain weight in the natural population. The TaGS3-7A-A allele was favoured in global modern wheat cultivars but the allelic frequency varied among different wheat-production regions of China, which indicated that this allele is of potential utility to improve wheat grain weight in certain wheat-production areas of China. CONCLUSIONS: The novel molecular information on wheat GS3 homologs and the KASP functional marker designed in this study may be useful in marker-assisted breeding for genetic improvement of wheat.


Asunto(s)
Clonación Molecular/métodos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Polimorfismo de Nucleótido Simple , Triticum/crecimiento & desarrollo , China , Frecuencia de los Genes , Estudios de Asociación Genética , Tamaño de los Órganos , Fenotipo , Filogenia , Proteínas de Plantas/química , Poliploidía , Dominios Proteicos , Sitios de Carácter Cuantitativo , Especificidad de la Especie , Triticum/genética , Triticum/metabolismo
12.
PLoS Genet ; 12(2): e1005844, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26848586

RESUMEN

Plants have evolved a considerable number of intrinsic tolerance strategies to acclimate to ambient temperature increase. However, their molecular mechanisms remain largely obscure. Here we report a DEAD-box RNA helicase, TOGR1 (Thermotolerant Growth Required1), prerequisite for rice growth themotolerance. Regulated by both temperature and the circadian clock, its expression is tightly coupled to daily temperature fluctuations and its helicase activities directly promoted by temperature increase. Located in the nucleolus and associated with the small subunit (SSU) pre-rRNA processome, TOGR1 maintains a normal rRNA homeostasis at high temperature. Natural variation in its transcript level is positively correlated with plant height and its overexpression significantly improves rice growth under hot conditions. Our findings reveal a novel molecular mechanism of RNA helicase as a key chaperone for rRNA homeostasis required for rice thermotolerant growth and provide a potential strategy to breed heat-tolerant crops by modulating the expression of TOGR1 and its orthologs.


Asunto(s)
Adaptación Fisiológica , Nucléolo Celular/enzimología , ARN Helicasas DEAD-box/metabolismo , Oryza/fisiología , Proteínas de Plantas/metabolismo , Precursores del ARN/metabolismo , Temperatura , Proliferación Celular , Ritmo Circadiano/genética , Mutación/genética , Oryza/citología , Oryza/enzimología , Desarrollo de la Planta , Precursores del ARN/genética , Procesamiento Postranscripcional del ARN/genética , Subunidades Ribosómicas Pequeñas/metabolismo
13.
PLoS Genet ; 12(7): e1006152, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27367609

RESUMEN

The sessile plants have evolved diverse intrinsic mechanisms to control their proper development under variable environments. In contrast to plastic vegetative development, reproductive traits like floral identity often show phenotypic robustness against environmental variations. However, it remains obscure about the molecular basis of this phenotypic robustness. In this study, we found that eg1 (extra glume1) mutants of rice (Oryza savita L.) showed floral phenotypic variations in different growth locations resulting in a breakdown of floral identity robustness. Physiological and biochemical analyses showed that EG1 encodes a predominantly mitochondria-localized functional lipase and functions in a high temperature-dependent manner. Furthermore, we found that numerous environmentally responsive genes including many floral identity genes are transcriptionally repressed in eg1 mutants and OsMADS1, OsMADS6 and OsG1 genetically act downstream of EG1 to maintain floral robustness. Collectively, our results demonstrate that EG1 promotes floral robustness against temperature fluctuation by safeguarding the expression of floral identify genes through a high temperature-dependent mitochondrial lipid pathway and uncovers a novel mechanistic insight into floral developmental control.


Asunto(s)
Flores/fisiología , Lipasa/genética , Mitocondrias/enzimología , Oryza/genética , Proteínas de Plantas/genética , Alelos , Ambiente , Regulación de la Expresión Génica de las Plantas , Genotipo , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Calor , Humanos , Lipasa/metabolismo , Lípidos/química , Mutación , Oryza/enzimología , Fenotipo , Proteínas de Plantas/metabolismo , Dominios Proteicos , Transcripción Genética , Transcriptoma
14.
PLoS Genet ; 9(3): e1003391, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23526892

RESUMEN

Heterotrimeric G proteins are an important group of signaling molecules found in eukaryotes. They function with G-protein-coupled-receptors (GPCRs) to transduce various signals such as steroid hormones in animals. Nevertheless, their functions in plants are not well-defined. Previous studies suggested that the heterotrimeric G protein α subunit known as D1/RGA1 in rice is involved in a phytohormone gibberellin-mediated signaling pathway. Evidence also implicates D1 in the action of a second phytohormone Brassinosteroid (BR) and its pathway. However, it is unclear how D1 functions in this pathway, because so far no partner has been identified to act with D1. In this study, we report a D1 genetic interactor Taihu Dwarf1 (TUD1) that encodes a functional U-box E3 ubiquitin ligase. Genetic, phenotypic, and physiological analyses have shown that tud1 is epistatic to d1 and is less sensitive to BR treatment. Histological observations showed that the dwarf phenotype of tud1 is mainly due to decreased cell proliferation and disorganized cell files in aerial organs. Furthermore, we found that D1 directly interacts with TUD1. Taken together, these results demonstrate that D1 and TUD1 act together to mediate a BR-signaling pathway. This supports the idea that a D1-mediated BR signaling pathway occurs in rice to affect plant growth and development.


Asunto(s)
Brasinoesteroides/metabolismo , Oryza , Reguladores del Crecimiento de las Plantas , Ubiquitina-Proteína Ligasas , Regulación de la Expresión Génica de las Plantas , Giberelinas/metabolismo , Proteínas de Unión al GTP Heterotriméricas/metabolismo , Oryza/genética , Oryza/crecimiento & desarrollo , Reguladores del Crecimiento de las Plantas/genética , Reguladores del Crecimiento de las Plantas/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Transducción de Señal/genética , Transducción de Señal/fisiología , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo
15.
Plant Cell ; 23(1): 396-411, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21258002

RESUMEN

Plants adapt their growth and development in response to perceived salt stress. Although DELLA-dependent growth restraint is thought to be an integration of the plant's response to salt stress, little is known about how histone modification confers salt stress and, in turn, affects development. Here, we report that floral initiator Shk1 kinase binding protein1 (SKB1) and histone4 arginine3 (H4R3) symmetric dimethylation (H4R3sme2) integrate responses to plant developmental progress and salt stress. Mutation of SKB1 results in salt hypersensitivity, late flowering, and growth retardation. SKB1 associates with chromatin and thereby increases the H4R3sme2 level to suppress the transcription of FLOWERING LOCUS C (FLC) and a number of stress-responsive genes. During salt stress, the H4R3sme2 level is reduced, as a consequence of SKB1 disassociating from chromatin to induce the expression of FLC and the stress-responsive genes but increasing the methylation of small nuclear ribonucleoprotein Sm-like4 (LSM4). Splicing defects are observed in the skb1 and lsm4 mutants, which are sensitive to salt. We propose that SKB1 mediates plant development and the salt response by altering the methylation status of H4R3sme2 and LSM4 and linking transcription to pre-mRNA splicing.


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Histonas/metabolismo , Precursores del ARN/metabolismo , Empalme del ARN , Ribonucleoproteínas Nucleares Pequeñas/metabolismo , Tolerancia a la Sal , Ácido Abscísico/farmacología , Arabidopsis/crecimiento & desarrollo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Flores/crecimiento & desarrollo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Proteínas de Dominio MADS/metabolismo , Metilación , Mutación , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN de Planta/metabolismo , Ribonucleoproteínas Nucleares Pequeñas/genética , Plantas Tolerantes a la Sal/genética , Plantas Tolerantes a la Sal/crecimiento & desarrollo , Plantas Tolerantes a la Sal/metabolismo , Transcripción Genética
16.
J Cancer Res Clin Oncol ; 150(6): 302, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38856753

RESUMEN

PURPOSE: Nowadays, cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have been approved for treating metastatic breast cancer and have achieved inspiring curative effects. But some discoveries have indicated that CDK 4/6 are not the requisite factors in some cell types because CDK2 partly compensates for the inhibition of CDK4/6. Thus, it is urgent to design CDK2/4/6 inhibitors for significantly enhancing their potency. This study aims to explore the mechanism of the binding of CDK2/4/6 kinases and their inhibitors to design novel CDK2/4/6 inhibitors for significantly enhancing their potency in different kinds of cancers. MATERIALS AND METHODS: A series of 72 disparately functionalized 4-substituted N-phenylpyrimidin-2-amine derivatives exhibiting potent inhibitor activities against CDK2, CDK4 and CDK6 were collected to apply to this research. The total set of these derivatives was divided into a training set (54 compounds) and a test set (18 compounds). The derivatives were constructed through the sketch molecule module in SYBYL 6.9 software. A Powell gradient algorithm and Tripos force field were used to calculate the minimal structural energy and the minimized structure was used as the initial conformation for molecular docking. By the means of 3D-QSAR models, partial least squares (PLS) analysis, molecular dynamics (MD) simulations and binding free energy calculations, we can find the relationship between structure and biological activity. RESULTS: In this study, we used molecular docking, 3D-QSAR and molecular dynamics simulation methods to comprehensively analyze the interaction and structure-activity relationships of 72 new CDK2/4/6 inhibitors. We used detailed statistical data to reasonably verify the constructed 3D-QSAR models for three receptors (q2 of CDK2 = 0.714, R2pred = 0.764, q2 = 0.815; R2pred of CDK4 = 0.681, q2 = 0.757; R2pred of CDK6 = 0.674). MD simulations and decomposition energy analysis validated the reasonability of the docking results and identified polar interactions as crucial factors that influence the different bioactivities of the studied inhibitors of CDK2/4/6 receptors, especially the electrostatic interactions of Lys33/35/43 and Asp145/158/163. The nonpolar interaction with Ile10/12/19 was also critical for the differing potencies of the CDK2/4/6 inhibitors. We concluded that the following probably enhanced the bioactivity against CDK2/4/6 kinases: (1) electronegative groups at the N1-position and electropositive and moderate-sized groups at ring E; (2) electrogroups featured at R2; (3) carbon atoms at the X-position or ring C replaced by a benzene ring; and (4) an electrogroup as R4. CONCLUSION: Previous studies, to our knowledge, only utilized a single approach of 3D-QSAR and did not integrate this method with other sophisticated techniques such as molecular dynamics simulations to discover new potential inhibitors of CDK2, CDK4, or CDK6. So we applied the intergenerational technology, such as 3D-QSAR technology, molecular docking simulation techniques, molecular dynamics simulations and MMPBSA19/MMGBSA20-binding free energy calculations to statistically explore the correlations between the structure with biological activities. The constructed 3D-QSAR models of the three receptors were reasonable and confirmed by the excellent statistical data. We hope the results obtained from this work will provide some useful references for the development of novel CDK2/4/6 inhibitors.


Asunto(s)
Quinasa 2 Dependiente de la Ciclina , Quinasa 4 Dependiente de la Ciclina , Quinasa 6 Dependiente de la Ciclina , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Inhibidores de Proteínas Quinasas , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/química , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 4 Dependiente de la Ciclina/química , Humanos , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacología , Quinasa 2 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 2 Dependiente de la Ciclina/química , Pirimidinas/química , Pirimidinas/farmacología , Relación Estructura-Actividad Cuantitativa
17.
Plant Mol Biol ; 81(3): 245-57, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23263858

RESUMEN

S-RNase-based self-incompatibility (SI) is an intraspecific reproductive barrier to prevent self-fertilization found in many species of the Solanaceae, Plantaginaceae and Rosaceae. In this system, S-RNase and SLF/SFB (S-locus F-box) genes have been shown to control the pistil and pollen SI specificity, respectively. Recent studies have shown that the SLF functions as a substrate receptor of a SCF (Skp1/Cullin1/F-box)-type E3 ubiquitin ligase complex to target S-RNases in Solanaceae and Plantaginaceae, but its role in Rosaceae remains largely undefined. Here we report the identification of two pollen-specific SLF-interacting Skp1-like (SSK) proteins, PbSSK1 and PbSSK2, in Pyrus bretschneideri from the tribe Pyreae of Rosaceae. Both yeast two-hybrid and pull-down assays demonstrated that they could connect PbSLFs to PbCUL1 to form a putative canonical SCF(SLF) (SSK/CUL1/SLF) complex in Pyrus. Furthermore, pull-down assays showed that the SSK proteins could bind SLF and CUL1 in a cross-species manner between Pyrus and Petunia. Additionally, phylogenetic analysis revealed that the SSK-like proteins from Solanaceae, Plantaginaceae and Rosaceae form a monoclade group, hinting their shared evolutionary origin. Taken together, with the recent identification of a canonical SCF(SFB) complex in Prunus of the tribe Amygdaleae of Rosaceae, our results show that a conserved canonical SCF(SLF/SFB) complex is present in Solanaceae, Plantaginaceae and Rosaceae, implying that S-RNase-based self-incompatibility shares a similar molecular and biochemical mechanism.


Asunto(s)
Proteínas de Plantas/metabolismo , Pyrus/genética , Ribonucleasas/metabolismo , Proteínas Ligasas SKP Cullina F-box/metabolismo , Autoincompatibilidad en las Plantas con Flores/fisiología , Alelos , Secuencia de Aminoácidos , ADN de Plantas/genética , Proteínas F-Box/genética , Proteínas F-Box/metabolismo , Flores/enzimología , Flores/genética , Flores/fisiología , Regulación de la Expresión Génica de las Plantas , Datos de Secuencia Molecular , Especificidad de Órganos , Petunia/genética , Petunia/metabolismo , Filogenia , Proteínas de Plantas/genética , Polen/enzimología , Polen/genética , Polen/fisiología , Unión Proteica , Pyrus/enzimología , Pyrus/fisiología , ARN de Planta/genética , Proteínas Recombinantes de Fusión , Ribonucleasas/genética , Proteínas Quinasas Asociadas a Fase-S/genética , Proteínas Quinasas Asociadas a Fase-S/metabolismo , Proteínas Ligasas SKP Cullina F-box/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Alineación de Secuencia , Técnicas del Sistema de Dos Híbridos
18.
Sci Adv ; 9(48): eadj4897, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-38019904

RESUMEN

Animals use past experience to guide future choices. The integration of experiences typically follows a hyperbolic, rather than exponential, decay pattern with a heavy tail for distant history. Hyperbolic integration affords sensitivity to both recent environmental dynamics and long-term trends. However, it is unknown how the brain implements hyperbolic integration. We found that mouse behavior in a foraging task showed hyperbolic decay of past experience, but the activity of cortical neurons showed exponential decay. We resolved this apparent mismatch by observing that cortical neurons encode history information with heterogeneous exponential time constants that vary across neurons. A model combining these diverse timescales recreated the heavy-tailed, hyperbolic history integration observed in behavior. In particular, the time constants of retrosplenial cortex (RSC) neurons best matched the behavior, and optogenetic inactivation of RSC uniquely reduced behavioral history dependence. These results indicate that behavior-relevant history information is maintained across multiple timescales in parallel and that RSC is a critical reservoir of information guiding decision-making.


Asunto(s)
Encéfalo , Giro del Cíngulo , Ratones , Animales , Giro del Cíngulo/fisiología , Corteza Cerebral/fisiología
19.
Front Behav Neurosci ; 17: 1111908, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37324523

RESUMEN

Computer vision has emerged as a powerful tool to elevate behavioral research. This protocol describes a computer vision machine learning pipeline called AlphaTracker, which has minimal hardware requirements and produces reliable tracking of multiple unmarked animals, as well as behavioral clustering. AlphaTracker pairs a top-down pose-estimation software combined with unsupervised clustering to facilitate behavioral motif discovery that will accelerate behavioral research. All steps of the protocol are provided as open-source software with graphic user interfaces or implementable with command-line prompts. Users with a graphical processing unit (GPU) can model and analyze animal behaviors of interest in less than a day. AlphaTracker greatly facilitates the analysis of the mechanism of individual/social behavior and group dynamics.

20.
Nat Commun ; 14(1): 7465, 2023 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-37978184

RESUMEN

Transposable elements (TEs) comprise ~85% of the common wheat genome, which are highly diverse among subgenomes, possibly contribute to polyploid plasticity, but the causality is only assumed. Here, by integrating data from gene expression cap analysis and epigenome profiling via hidden Markov model in common wheat, we detect a large proportion of enhancer-like elements (ELEs) derived from TEs producing nascent noncoding transcripts, namely ELE-RNAs, which are well indicative of the regulatory activity of ELEs. Quantifying ELE-RNA transcriptome across typical developmental stages reveals that TE-initiated ELE-RNAs are mainly from RLG_famc7.3 specifically expanded in subgenome A. Acquisition of spike-specific transcription factor binding likely confers spike-specific expression of RLG_famc7.3-initiated ELE-RNAs. Knockdown of RLG_famc7.3-initiated ELE-RNAs resulted in global downregulation of spike-specific genes and abnormal spike development. These findings link TE expansion to regulatory specificity and polyploid developmental plasticity, highlighting the functional impact of TE-driven regulatory innovation on polyploid evolution.


Asunto(s)
Elementos Transponibles de ADN , Triticum , Elementos Transponibles de ADN/genética , Triticum/genética , Regulación de la Expresión Génica , Poliploidía , Transcriptoma , ARN
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