Gene Expression Correlation Analysis Reveals MYC-NAC Regulatory Network in Cotton Pigment Gland Development.
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ABSTRACT:
SUBMITTER: Cheng H
PROVIDER: S-EPMC8125883 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:In seeds and other parts of cultivated, tetraploid cotton (Gossypium hirsutum L.), multicellular groups of cells lysigenously form dark glands containing toxic terpenoids such as gossypol that defend the plant against pests and pathogens. Using RNA-seq analysis of embryos from near-isogenic glanded (Gl2 Gl2 Gl3 Gl3 ) versus glandless (gl2 gl2 gl3 gl3 ) plants, we identified 33 genes that expressed exclusively or at higher levels in embryos just prior to gland formation in glanded plants. Virus-induced gene silencing against three gene pairs led to significant reductions in the number of glands in the leaves, and significantly lower levels of gossypol and related terpenoids. These genes encode transcription factors and have been designated the 'Cotton Gland Formation' (CGF) genes. No sequence differences were found between glanded and glandless cotton for CGF1 and CGF2 gene pairs. The glandless cotton has a transposon insertion within the coding sequence of the GoPGF (synonym CGF3) gene of the A subgenome and extensive mutations in the promoter of D subgenome homeolog. Overexpression of GoPGF (synonym CGF3) led to a dramatic increase in gossypol and related terpenoids in cultured cells, whereas CRISPR/Cas9 knockout of GoPGF (synonym CGF3) genes resulted in glandless phenotype. Taken collectively, the results show that the GoPGF (synonym CGF3) gene plays a critical role in the formation of glands in the cotton plant. Seed-specific silencing of CGF genes, either individually or in combination, could eliminate glands, thus gossypol, from the cottonseed to render it safe as food or feed for monogastrics.
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Project description:At present, the etiology and pathogenesis of recurrent early pregnancy loss (REPL) are not completely clear. Therefore, identifying the underlying diagnostic and prognostic biomarkers of REPL can provide new ideas for the diagnosis and treatment of REPL. The chip data of REPL (GSE63901) were downloaded from the NCBI Gene Expression Omnibus (GEO) database. Weighted Gene Co-Expression Network Analysis (WGCNA) was used to construct a co-expression module for studying the relationship between gene modules and clinical features. In addition, functional analysis of hub genes in modules of interest was performed. A total of 23 co-expression modules were identified, two of which were most significantly associated with three clinical features. The MEbrown module was positively correlated with cyclin E level and the out-of-phase trait while the MEred module was positively correlated with the effect of progesterone. We identified 17 hub genes in the MEred module. The functional enrichment analysis indicated that such hub genes were mainly involved in pathways related to cellular defense response and natural killer (NK) cell-mediated cytotoxicity. In the MEbrown module, we identified 19 hub genes, which were mainly enriched in cell adhesion molecule production, regulation of cellular response to growth factor stimulus, epithelial cell proliferation, and transforming growth factor-β (TGF-β) signaling pathway. In addition, the hub genes were validated by using other datasets and three true hub genes were finally obtained, namely DOCK2 for the MEred module, and TRMT44 and ERVMER34-1 for the MEbrown module. In conclusion, our results screened potential biomarkers that might contribute to the diagnosis and treatment of REPL.
| S-EPMC7295631 | biostudies-literature
Project description:BackgroundTranscription factors operate as important switches of transcription networks, and NAC (NAM, ATAF, and CUC) transcription factors are a plant-specific family involved in multiple biological processes. However, this gene family has not been systematically characterized in cotton.ResultsHere we identify a large number of genes with conservative NAC domains in four cotton species, with 147 found in Gossypium arboreum, 149 in G. raimondii, 267 in G. barbadense and 283 in G. hirsutum. Predicted membrane-bound NAC genes were also identified. Phylogenetic analysis showed that cotton NAC proteins clustered into seven subfamilies and homologous protein pairs showed similar characteristics. Evolutionary property analysis revealed that purifying selection of NAC genes occurred between diploid and polyploid cotton species, and variation analysis showed GhNAC genes may have been subjected to selection and domestication. NAC proteins showed extensive transactivation and this was dependent on the C-terminus. Some development and stress related cis-elements were enriched in the promoters of GhNAC genes. Comprehensive expression analysis indicated that 38 GhNAC genes were candidates for involvement in fiber development, and 120 in stress responses. Gene co-expression network analysis revealed relationships between fiber-associated NAC genes and secondary cell wall (SCW) biosynthesis genes.ConclusionsNAC genes were identified in diploid and tetraploid cotton, revealing new insights into their evolution, variation and homology relationships. Transcriptome analysis and co-expression network indicated roles for GhNAC genes in cotton fiber development and stress response, and NAC genes may prove useful in molecular breeding programmes.
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Project description:Brassinosteroids (BRs) participate in the regulation of plant growth and development through BRI1-EMS-SUPPRESSOR1 (BES1)/BRASSINAZOLE-RESISTANT1 (BZR1) family transcription factors. Cotton (Gossypium hirsutum) fibers are highly elongated single cells, and BRs play a vital role in the regulation of fiber elongation. However, the mode of action on how BR is involved in the regulation of cotton fiber elongation remains unexplored. Here, we generated GhBES1.4 over expression lines and found that overexpression of GhBES1.4 promoted fiber elongation, whereas silencing of GhBES1.4 reduced fiber length. DNA affinity purification and sequencing (DAP-seq) identified 1,531 target genes of GhBES1.4, and five recognition motifs of GhBES1.4 were identified by enrichment analysis. Combined analysis of DAP-seq and RNA-seq data of GhBES1.4-OE/RNAi provided mechanistic insights into GhBES1.4-mediated regulation of cotton fiber development. Further, with the integrated approach of GWAS, RNA-seq, and DAP-seq, we identified seven genes related to fiber elongation that were directly regulated by GhBES1.4. Of them, we showed Cytochrome P450 84A1 (GhCYP84A1) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase 1 (GhHMG1) promote cotton fiber elongation. Overall, the present study established the role of GhBES1.4-mediated gene regulation and laid the foundation for further understanding the mechanism of BR participation in regulating fiber development.
| S-EPMC10022633 | biostudies-literature
Project description:Myc-deficient mice fail to develop normal vascular networks and Myc-deficient embryonic stem cells fail to provoke a tumor angiogenic response when injected into immune compromised mice. However, the molecular underpinnings of these defects are poorly understood. To assess whether Myc indeed contributes to embryonic vasculogenesis we evaluated Myc function in Xenopus laevis embryogenesis. Here, we report that Xc-Myc is required for the normal assembly of endothelial cells into patent vessels during both angiogenesis and lymphangiogenesis. Accordingly, the specific knockdown of Xc-Myc provokes massive embryonic edema and hemorrhage. Conversely, Xc-Myc overexpression triggers the formation of ectopic vascular beds in embryos. Myc is required for normal expression of Slug/Snail2 and Twist, and either XSlug/Snail2 or XTwist could compensate for defects manifest by Xc-Myc knockdown. Importantly, knockdown of Xc-Myc, XSlug/Snail2 or XTwist within the lateral plate mesoderm, but not the neural crest, provoked embryonic edema and hemorrhage. Collectively, these findings support a model in which Myc, Twist and Slug/Snail2 function in a regulatory circuit within lateral plate mesoderm that directs normal vessel formation in both the vascular and lymphatic systems.
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Project description:Background and objectivesSepsis is a leading cause of mortality and morbidity in the intensive care unit. Regulatory mechanisms underlying the disease progression and prognosis are largely unknown. The study aimed to identify master regulators of mortality-related modules, providing potential therapeutic target for further translational experiments.MethodsThe dataset GSE65682 from the Gene Expression Omnibus (GEO) database was utilized for bioinformatic analysis. Consensus weighted gene co-expression netwoek analysis (WGCNA) was performed to identify modules of sepsis. The module most significantly associated with mortality were further analyzed for the identification of master regulators of transcription factors and miRNA.ResultsA total number of 682 subjects with various causes of sepsis were included for consensus WGCNA analysis, which identified 27 modules. The network was well preserved among different causes of sepsis. Two modules designated as black and light yellow module were found to be associated with mortality outcome. Key regulators of the black and light yellow modules were the transcription factor CEBPB (normalized enrichment score = 5.53) and ETV6 (NES = 6), respectively. The top 5 miRNA regulated the most number of genes were hsa-miR-335-5p (n = 59), hsa-miR-26b-5p (n = 57), hsa-miR-16-5p (n = 44), hsa-miR-17-5p (n = 42), and hsa-miR-124-3p (n = 38). Clustering analysis in 2-dimension space derived from manifold learning identified two subclasses of sepsis, which showed significant association with survival in Cox proportional hazard model (p = 0.018).ConclusionsThe present study showed that the black and light-yellow modules were significantly associated with mortality outcome. Master regulators of the module included transcription factor CEBPB and ETV6. miRNA-target interactions identified significantly enriched miRNA.
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Project description:Pigment glands, also known as black glands or gossypol glands, are specific for Gossypium spp. These glands strictly confine large amounts of secondary metabolites to the lysigenous cavity, leading to the glands' intense colour and providing defence against pests and pathogens. This study performed a comparative transcriptome analysis of glanded versus glandless cotton cultivars. Twenty-two transcription factors showed expression patterns associated with pigment glands and were characterized. Phenotypic screening of the genes, via virus-induced gene silencing, showed an apparent disappearance of pigmented glands after the silencing of a pair of homologous MYB-encoding genes in the A and D genomes (designated as CGP1). Further study showed that CGP1a encodes an active transcription factor, which is specifically expressed in the gland structure, while CGP1d encodes a non-functional protein due to a fragment deletion, which causes premature termination. RNAi-mediated silencing and CRISPR knockout of CGP1 in glanded cotton cultivars generated a glandless-like phenotype, similar to the dominant glandless mutant Gl2 e . Microscopic analysis showed that CGP1 knockout did not affect gland structure or density, but affected gland pigmentation. The levels of gossypol and related terpenoids were significantly decreased in cgp1 mutants, and a number of gossypol biosynthetic genes were strongly down-regulated. CGP1 is located in the nucleus where it interacts with GoPGF, a critical transcription factor for gland development and gossypol synthesis. Our data suggest that CGP1 and GoPGF form heterodimers to control the synthesis of gossypol and other secondary metabolites in cotton.
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Project description:Target gene identification for transcription factors is a prerequisite for the systems wide understanding of organismal behaviour. NAM-ATAF1/2-CUC2 (NAC) transcription factors are amongst the largest transcription factor families in plants, yet limited data exist from unbiased approaches to resolve the DNA-binding preferences of individual members. Here, we present a TF-target gene identification workflow based on the integration of novel protein binding microarray data with gene expression and multi-species promoter sequence conservation to identify the DNA-binding specificities and the gene regulatory networks of 12 NAC transcription factors. Our data offer specific single-base resolution fingerprints for most TFs studied and indicate that NAC DNA-binding specificities might be predicted from their DNA-binding domain's sequence. The developed methodology, including the application of complementary functional genomics filters, makes it possible to translate, for each TF, protein binding microarray data into a set of high-quality target genes. With this approach, we confirm NAC target genes reported from independent in vivo analyses. We emphasize that candidate target gene sets together with the workflow associated with functional modules offer a strong resource to unravel the regulatory potential of NAC genes and that this workflow could be used to study other families of transcription factors.
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Project description:BACKGROUND: The transcriptional regulator c-Myc is the most frequently deregulated oncogene in human tumors. Targeted overexpression of this gene in mice results in distinct types of lung adenocarcinomas. By using microarray technology, alterations in the expression of genes were captured based on a female transgenic mouse model in which, indeed, c-Myc overexpression in alveolar epithelium results in the development of bronchiolo-alveolar carcinoma (BAC) and papillary adenocarcinoma (PLAC). In this study, we analyzed exclusively the promoters of induced genes by different in silico methods in order to elucidate the c-Myc transcriptional regulatory network. RESULTS: We analyzed the promoters of 361 transcriptionally induced genes with respect to c-Myc binding sites and found 110 putative binding sites in 94 promoters. Furthermore, we analyzed the flanking sequences (+/- 100 bp) around the 110 c-Myc binding sites and found Ap2, Zf5, Zic3, and E2f binding sites to be overrepresented in these regions. Then, we analyzed the promoters of 361 induced genes with respect to binding sites of other transcription factors (TFs) which were upregulated by c-Myc overexpression. We identified at least one binding site of at least one of these TFs in 220 promoters, thus elucidating a potential transcription factor network. The analysis correlated well with the significant overexpression of the TFs Atf2, Foxf1a, Smad4, Sox4, Sp3 and Stat5a. Finally, we analyzed promoters of regulated genes which where apparently not regulated by c-Myc or other c-Myc targeted TFs and identified overrepresented Oct1, Mzf1, Ppargamma, Plzf, Ets, and HmgIY binding sites when compared against control promoter background. CONCLUSION: Our in silico data suggest a model of a transcriptional regulatory network in which different TFs act in concert upon c-Myc overexpression. We determined molecular rules for transcriptional regulation to explain, in part, the carcinogenic effect seen in mice overexpressing the c-Myc oncogene.
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Project description:MicroRNAs are endogenous ~22 nt RNAs that regulate gene expression by translational inhibition and mRNA destabilization. MicroRNA-29b (miR-29b) is essential for progression of mouse embryos past preimplantation development; however, details of the underlying regulatory network remain to be elucidated. Here, we used RNA sequencing to identify changes in the transcriptome of mouse embryos in response to miR-29b inhibition. Morula-stage embryos that had been subject to miR-29b inhibition throughout preimplantation development exhibited significant expression changes in 870 genes compared with controls. Among 405 genes that were downregulated, 30 genes encoded factors with known essential function during early embryonic development, including the pluripotent stem cell factor Nanog. We identified 19 genes encoding putative miR-29b target transcripts. These included Zbtb40, Hbp1, Ccdc117, Ypel2, Klf4, and Tmed9, which are upregulated at the 4-cell state of mouse development concomitant with miR-29b downregulation. Luciferase reporter analysis confirmed that Zbtb40, Hbp1, Ccdc117, Ypel2, and Klf4 transcripts are direct targets of miR-29b. These results suggest that miR-29b decreases the mRNA levels of several target genes during early mouse development, including the gene encoding the reprogramming factor Klf4. We hypothesize that inhibition of miR-29b causes overexpression of its target genes, triggering downstream signaling networks to decrease the expression of genes that are essential for embryonic development. In conclusion, miR-29b controls an extensive regulatory network in early mouse embryos, which comprises reprogramming factors and molecular regulators of post-transcriptional modification processes.
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