Molecular Genetics and Genomics最新文献

R2R3-MYBs constitute one of the largest families of plant transcription factors and several members are involved in the regulation of distinct branches of the phenylpropanoid pathway, acting as activators or repressors of the biosynthesis of a plethora of specialized metabolites. Although R2R3-MYBs have been extensively characterized as regulators of lignin deposition in distinct cellular contexts and species, still little is known about their roles in regulating specific aspects of grass lignification. Here, we report on the genome-wide characterization of the R2R3-MYB family in the model grass Setaria viridis and identification of members potentially involved in the regulation of lignin/tricin metabolism. A total of 132 genes encoding R2R3-MYBs were found in S. viridis, which clustered in 43 well-supported subgroups. Comprehensive in silico expression, co-expression, and RT-qPCR analyses allowed the identification of 4 candidate SvMYBs that showed (i) similar expression profiles to that observed for lignin biosynthetic genes in a set of different organs/conditions of S. viridis; (ii) similar expression patterns to that of lignin biosynthetic genes along the S. viridis elongating internode; (iii) co-expression with several phenylpropanoid- and lignin-related genes in public transcriptomic databases; (iv) high expression levels in the top of the S. viridis elongating internode, a tissue undergoing active lignification. Three of these SvMYBs activated the promoters of lignin and tricin biosynthetic genes in transactivation assays using tobacco protoplasts. Altogether, our results suggest that these three transcription factors control grass-specific aspects of lignin deposition and further studies might confirm their ability to control lignin deposition and tricin metabolism in S. viridis.

Grain quality traits such as kernel hardness index (KHI), kernel diameter (KD), and thousand grain weight (TGW) are pivotal determinants of processing quality and yield potential in bread wheat (Triticum aestivum L.). In this study, we performed a comprehensive genome-wide association study (GWAS) using eight advanced multi-locus models implemented in GAPIT v3.0 to dissect the genetic architecture underlying these traits across 225 spring wheat genotypes evaluated under two distinct environments. A total of 739 significant quantitative trait nucleotides (QTNs) were identified across all datasets using eight different models, with the most QTNs detected by the BLINK and FarmCPU models. Thirty-six common QTNs were detected by all models across traits, including stable QTNs for KHI, KD, and TGW, with several showing pleiotropic effects. Notably, 13 QTNs for KHI were consistently detected across environments, underscoring their potential for marker-assisted selection (MAS). Comparative analysis revealed that 8 QTNs overlapped with previously reported QTLs, particularly for KHI and TGW, thereby validating their reliability. In contrast, no overlaps were observed for KD, suggesting novel loci for this trait. Five highly promising QTNs were prioritized based on stability, multi-trait associations, and detection consistency. Candidate gene analysis revealed 1,916 genes associated with KHI, KD, and TGW, with functional annotation indicating enrichment of domains related to lipid metabolism (GDSL esterases), signalling (protein kinases), assimilate transport (CRAL-TRIO and sucrose transporters), and cell-wall modification (expansins). Differential in-silico expression across grain-related tissues supported their functional relevance. Analysis of 36 common MTAs refined a subset of 95 candidate genes representing key regulatory pathways underlying grain quality traits. The stable QTNs and biologically relevant candidate genes identified in this study provide valuable resources for fine-mapping, MAS, and functional validation, which may support the development of high-yielding wheat cultivars with improved grain quality.

The APOE4 is a well-established and significant genetic risk factor associated with the accumulation of β-amyloid (Aβ) plaques and hyperphosphorylated tau (p-tau) in the pathogenesis of Alzheimer's disease (AD). Our previous research has implicated circular RNA FoxO3 (circ-FoxO3) in the clearance of aggregated proteins in ischemic stroke. However, the role of circ-FoxO3 in the accumulation of abnormal proteins during AD development remains unclear. In this study, we demonstrate that circ-FoxO3 mitigates APOE4-driven neurotoxic protein aggregation by enhancing FoxO3-mediated autophagy. Specifically, transgenic mice expressing human APOE4 exhibited elevated levels of p-tau and Aβ, and these pathological alterations were significantly ameliorated by circ-FoxO3. Mechanistically, we found that circ-FoxO3 upregulates its host gene FoxO3, leading to activation of autophagy and subsequent clearance of neurotoxic protein aggregates. The findings highlight a critical role for circ-FoxO3 in counteracting APOE4-induced brain damage and suggest its potential as a therapeutic target for mitigating APOE4-related neuropathology.

Psychological stress is increasingly recognized as an important determinant of human skin health, but the molecular and epigenetic mechanisms by which it affects the epidermis are still not well understood. To investigate whether psychological stress is associated with molecular differences in the epidermis, and how these might relate to skin phenotypes, we performed a multi-omics study in 60 stressed and 60 relaxed young adults. From lower-back epidermal samples, we generated DNA methylation profiles and RNA-seq data, and additionally measured skin cytokines and skin phenotypes. We identified 289 differentially methylated probes and 10 differentially expressed genes associated with psychological stress. Integration of methylation and expression with a functional epigenetic module approach yielded seven network modules; enrichment analyses of DMP-annotated genes and module genes revealed significant enrichment of terms related to glutamatergic synapse and synaptic signaling, in line with the emerging concept of a cutaneous neuroendocrine system. None of the 36 tested skin cytokines differed significantly between groups after correction for multiple testing. Skin darkening scores were higher in the stressed group. A CpG site in the SERPINA1 promoter and SERPINA1 expression were associated with this phenotype, and mediation analysis suggested that SERPINA1 expression partly mediated the association between cg01431455 methylation and skin darkening. Taken together, our study links psychological stress to coordinated differences in epidermal DNA methylation and gene expression, highlights glutamatergic and SERPINA1-related pathways as candidates for further mechanistic study, and establishes an epidermal multi-omics dataset for future work on stress-skin interactions.

Sesame, one of the earliest cultivated oil crops in human history, holds a distinguished place due to its high oil content, rich flavor, and distinctive nutty aroma. In this study, we performed whole-genome resequencing on five Egyptian sesame genotypes (Shandaweel 3, Toshky1, and three gamma-irradiated mutant lines). Additionally, we incorporated 19 publicly available sesame genome datasets from the NCBI Sequence Read Archive (SRA) to support comparative genomic analyses. We identified 6,106,085 nucleotide variants across the 24 sesame genotypes studied. After excluding low-coverage SNPs, we obtained 26,424 SNPs with MAF > 0.05 used for subsequent analysis. The highest number of SNPs was observed on Chromosome Si01 (4144 SNPs), followed by Si12 (3721 SNPs) and Si13 (3151 SNPs), whereas Si09 (241 SNPs) and Si02 (359 SNPs) displayed the lowest SNP counts. Genome-wide diversity analysis revealed variation across chromosomes, with chromosomes Si04 and Si07 showing the highest heterozygosity (Ho = 0.816-0.849) and polymorphism information content (PIC = 0.347-0.353). Population structure analysis identified three distinct genetic clusters, with Egyptian cultivars forming a genetically pure and separate cluster.Chinese cultivars showed admixture with those from the USA and South Korea. Phylogenetic analysis supported the country-based clustering, with Egyptian genotypes forming a unique group. SNP effect analysis showed that missense mutations were common, potentially affecting protein function. Notable impacted genes included AXR1, CYP73A5, and CERK1, which play critical roles in growth, stress resilience, and pathogen defense. By integrating public RNA-seq datasets with our genomic variant data, we explored the correlation between gene expression and genetic variation. This multi-omics analysis identified genes with variants and expression patterns potentially involved in stress adaptation, including membrane stabilizers (UGT80B1, CalS10), signaling regulators (PUB9, CNGC15b), hormonal integrators (ARF2, DLO1), and redox managers. Our whole-genome sequencing study highlights the influence of geographic origin on sesame genetic diversity and provides SNP data for breeding programs aimed at enhancing adaptability and resilience.

Chemical carcinogen induced mouse models closely mimic environmentally driven human cancers and provide platforms for studying tumor initiation and progression. However, the behavior and diagnostic value of cell-free DNA (cfDNA) in such models remain poorly understood, limiting their translational utility for biomarker development. Considering the increasing clinical relevance of cfDNA for early detection and treatment monitoring, this study aimed to systematically characterize cfDNA dynamics and genomic alterations in B(a)P induced lung cancer and DMH induced colon cancer mouse models. The aim was to evaluate cfDNA as a minimally invasive biomarker that reflects tumor burden and its potential use in preclinical diagnostic and therapeutic studies. Mouse lung and colon cancers were induced using B(a)P and DMH, respectively. Plasma was collected at defined time points, cfDNA was isolated, quantified, and analyzed for integrity profiles. Real time assessment was performed using liquid biopsies of cell free DNA using NGS-WGS platform for non-invasive tumor detection in live animals, reserving histopathology for post-mortem analysis. Our results reveal circulating cell-free DNA mutations similar to those found in humans (Lung cancer: ALK, NRAS, NF1, BRAF, FGFR1OP, FGFR1, STK11ip, AKT1 & AK1S1; Colon cancer: APC, MYC, KRAS). We have performed gene enrichment and protein-protein interactions and found various cancer related genes. The histopathological examination revealed neoplastic changes that corroborated with genomic studies. This study establishes cfDNA as a potential surrogate biomarker in chemical carcinogen induced lung and colon cancer models, supporting its utility for early detection, disease monitoring, and preclinical therapeutic assessment.