BMC Genomics最新文献

Background: The regulation of chromatin accessibility is essential in eukaryotic cells as one of several mechanisms that ensure gene activation occurs at appropriate times and in appropriate cell types. Accordingly, mutations in chromatin remodeling proteins are linked to many different developmental disorders and cancers. One example of a chromatin protein that has been linked to both developmental abnormalities and cancer is BPTF/NURF301, the largest subunit of the Nucleosome Remodeling Factor (NuRF) complex. The BPTF subunit is not only important for the formation of NuRF but also helps direct its activity to particular regions of chromatin by preferentially binding histone H3 lysine four trimethylation (H3K4me3). Notably, defects caused by knockdown of bptf in Xenopus embryos mimic those caused by knockdown of wdr5, a core subunit of all H3K4me3 methyltransferase complexes. However, the mechanistic details of how and where BPTF/NuRF is recruited to regulate gene expression vary between studies and have been largely tested in vitro and/or in cultured cells. Improving our understanding of how this chromatin remodeling complex targets specific gene loci and regulates their expression in an organismal context will provide important insight into how pathogenic mutations disrupt its normal, in vivo, cellular functions.

Results: Here, we report our findings on the role of BPTF in maintaining chromatin accessibility and essential function in planarian (Schmidtea mediterranea) stem cells. We find that depletion of planarian BPTF primarily affects accessibility at gene promoters near transcription start sites (TSSs). BPTF-dependent loss of accessibility did not correlate with decreased gene expression when we considered all affected loci. However, we found that genes marked by Set1-dependent H3K4me3, but not MLL1/2-dependent H3K4me3, showed increased sensitivity to the loss of BPTF-dependent accessibility. In addition, knockdown of bptf (Smed-bptf) produces loss-of-function phenotypes similar to those caused by knockdown of Smed-set1.

Conclusions: The S.mediterranea homolog of NuRF protein BPTF (SMED-BPTF) is essential for normal homeostasis in planarian tissues, potentially through its role in maintaining chromatin accessibility at a specific subset of gene promoters in planarian stem cells. By identifying loci that lose both chromatin accessibility and gene expression after depletion of BPTF, we have identified a cohort of genes that may have important functions in stem cell biology.

Background: Intramuscular fat (IMF) not only directly affects the tenderness, juiciness, and overall flavour of meat but also plays a significant role in influencing consumer preferences for pork. Therefore, exploring key biomarkers that influence IMF deposition is highly important for breeding high-quality pork. IMF is a typical quantitative trait that is regulated by the interaction of multiple coding and noncoding RNAs. Traditional differential analysis methods typically focus on individual genes, making it difficult to identify key genes and their underlying mechanisms accurately. Weighted gene coexpression network analysis (WGCNA) is an efficient and accurate method for identifying and characterizing key pathways and genes associated with complex traits. Therefore, the aim of this study was to construct an mRNA‒lncRNA coexpression network related to IMF using WGCNA to explore and identify potential candidate genes that influence IMF in pigs.

Results: Full-length transcriptome sequencing was performed on 31 220-day-old Jiangquan black pigs raised in the same environment, and a gene expression matrix comprising 25,609 genes was constructed. Nine coexpression modules were identified through WGCNA, with the number of genes in these modules ranging from 33 to 3648. The magenta module (corr = 0.7, P < 0.01) and the turquoise module (corr = -0.77, P < 0.01) were significantly associated with IMF deposition. Hub genes in each module were identified on the basis of the screening criteria of GS > 0.4 and MM > 0.8. Combined with enrichment analysis and protein‒protein interaction (PPI) analysis, 18 key mRNAs potentially related to IMF were selected: CRKL, CBL, PDGFRB, DOCK1, YWHAH, HSP90AB1, LOC100524873, NDUFA1, NDUFA11, NDUFA12, NDUFA2, NDUFAB1, NDUFB10, NDUFB3, NDUFB7, NDUFS5, NDUFS6, and UQCR10. To explore the regulatory role of lncRNAs in the process of IMF deposition, we constructed an lncRNA‒mRNA‒pathway network on the basis of the relationships between lncRNAs and key mRNAs, as well as the results of Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. This network includes four key lncRNAs (TGOLN2, LOC100521518, LOC100524915, and LOC100622481) and predicts the potential mechanisms by which lncRNAs regulate IMF deposition.

Conclusions: Through WGCNA, enrichment analysis, and PPI analysis, 18 mRNAs and four lncRNAs potentially involved in IMF deposition were identified, and the lncRNA regulatory pathways were preliminarily explored. Our findings provide new insights into the regulatory mechanisms of pig IMF deposition and lay the foundation for further exploration of the molecular mechanisms underlying pig fat deposition.

Water spinach (Ipomoea aquatica Forsk.) is an important leaf vegetable affected by salt stress, however, little is known about its salt adaption mechanism. Here, we integrated physiomics, ionomics, transcriptomics, and metabolomics to analyze the root adaptation response of two water spinach varieties, BG (salt-tolerant) and MF (salt-sensitive), at 150 mM NaCl. The results showed that compared with MF, BG significantly reduced the content of malondialdehyde (MDA) and H₂O₂, and increased catalase (CAT) activity and proline content. Ionome analysis demonstrated that BG significantly reduced Na⁺ accumulation and increased K⁺ level to reduce the toxicity of Na⁺, compared to MF. Weighted gene co-expression network analysis (WGCNA) revealed that key transcription factors such as HSFA4A, bHLH093, and IDD7, which were only up-regulated in BG. Multi-omics revealed that BG reprogrammed key pathways: starch and sucrose metabolism, as well as galactose metabolism, leading to decreased amylose production and increased sucrose and galactose levels, helping to maintain cellular osmotic balance in response to salt stress. These findings provide insight into transcriptional regulation in response to salt stress, which could advance the genetic enhancement of water spinach.

Space travel is a growing area of interest and includes initiatives such as NASA's Moon-to-Mars Mission. Reports on the cardiovascular effects of space travel reveal changes in morphology, metabolism, and function of the cardiovascular system. In this study, the cardiovascular response to immunization in space was studied in mice which were housed and immunized while on the International Space Station (ISS). Mice were immunized with tetanus toxoid combined with the adjuvant CpG (TT + CpG) and the effects of vaccination in space were studied using transcriptomics. Analysis of the mouse heart transcriptome was performed on flight control and flight-immunized mice. The results show that immunization aboard the ISS stimulates heightened inflammation in the heart via induction of the nuclear factor kappa B (NF-κB) signaling pathway to promote the release of the pro-inflammatory cytokines IFNγ, IL-17 and IL-6. Additional transcriptomic changes included alterations in the cytoskeleton and in the expression of transcripts associated with protection from oxidative stress. In summary, inflammation in the heart can occur following immunization in space. This investigation explores the impact of immune challenges on the heart and lays the groundwork for future research into additional cardiac alterations which can occur during spaceflight.

The brine shrimp Artemia, a crustacean adapted to the extreme conditions of hypersaline environments, comprises nine regionally distributed sexual species scattered (island-like) over heterogeneous environments and asexual (parthenogenetic) lineages with different ploidies. Such sexual and asexual interaction within the genus raises questions regarding the origin and time of divergence of both sexual species and asexual lineages, including the persistence of the latter over time, a problem not yet clarified using single mitochondrial and nuclear markers. Based on the complete mitochondrial genome of all species and parthenogenetic lineages, this article first describes the mitogenomic characteristics (nucleotide compositions, genome mapping, codon usage, and tRNA secondary structure) of sexual species and asexual types and, secondly, it provides a comprehensive updated phylogenetic analysis. Molecular dating and geographical evidence suggest that the ancestral Artemia taxon originated in ca. 33.97 Mya during the Paleogene Period. The mitogenomic comparisons suggest that the common ancestor of diploid and triploid parthenogenetic lineages (ca. 0.07 Mya) originated from a historical ancestor (ca. 0.61 Mya) in the Late Pleistocene. Additionally, the common ancestor of tetraploid and pentaploid parthenogenetic lineages (ca. 0.05 Mya) diverged from a historical maternal ancestor with A. sinica (ca. 0.96 Mya) in the early Pleistocene. The parthenogenetic lineages do not share a direct ancestor with any sexual species. The Asian clade ancestor diverged more recently (ca. 14.27 Mya, Middle Miocene). The mitogenomic characteristics, maternal phylogenetic tree, and especially divergence time prove that A. monica and A. franciscana are two biological species.

Background: Few cohorts have study populations large enough to conduct molecular analysis of ex vivo lung tissue for genomic analyses. Transcriptome imputation is a non-invasive alternative with many potential applications. We present a novel transcriptome-imputation method called the Lung Gene Expression and Network Imputation Engine (LungGENIE) that uses principal components from blood gene-expression levels in a linear regression model to predict lung tissue-specific gene-expression.

Methods: We use paired blood and lung RNA sequencing data from the Genotype-Tissue Expression (GTEx) project to train LungGENIE models. We replicate model performance in a unique dataset, where we generated RNA sequencing data from paired lung and blood samples available through the SUNY Upstate Biorepository (SUBR). We further demonstrate proof-of-concept application of LungGENIE models in an independent blood RNA sequencing data from the Genetic Epidemiology of COPD (COPDGene) study.

Results: We show that LungGENIE prediction accuracies have higher correlation to measured lung tissue expression compared to existing cis-expression quantitative trait loci-based methods (median Pearson's r = 0.25, IQR 0.19-0.32), with close to half of the reliably predicted transcripts being replicated in the testing dataset. Finally, we demonstrate significant correlation of differential expression results in chronic obstructive pulmonary disease (COPD) from imputed lung tissue gene-expression and differential expression results experimentally determined from lung tissue.

Conclusion: Our results demonstrate that LungGENIE provides complementary results to existing expression quantitative trait loci-based methods and outperforms direct blood to lung results across internal cross-validation, external replication, and proof-of-concept in an independent dataset. Taken together, we establish LungGENIE as a tool with many potential applications in the study of lung diseases.

Background: Cell differentiation during development is orchestrated by precisely coordinated gene expression programs. While some regulatory mechanisms are well understood, there is a significant room to explore unresolved aspects of lineage choice and cell-fate decisions, as many events in these processes are still not fully elucidated. Given that, gene expression is influenced not only by transcriptional control but also by post-transcriptional events. Here, we described the presence of post-transcriptional regulation on gene expression during lineage commitment across all three embryonic germ layers. We employed monolayer differentiation protocols to map early transcriptional and post-transcriptional events in human embryonic stem cell specification. This approach included obtaining representative populations from the three germ layers, followed by sequencing of both polysome-bound and total RNAs.

Results: We characterized our model by its unique expression profile and the presence of specific markers for each differentiation. RNA sequencing revealed a consistent pattern of gene upregulated and downregulated when comparing the transcriptome and translatome during the differentiation of all three germ layers. By comparing these datasets, we identified genes subjected to post-transcriptional regulation in all germ layer differentiations and categorized the nature of this regulation. GO analysis demonstrated that polysome profiling serves as a complementary technique, capturing nuances that may be overlooked when analyzing only the transcriptome. Finally, we directly compared the transcriptome and translatome to identify genes actively recruited to the translation machinery, uncovering unique features specific to each germ layer.

Conclusions: Substantial post-transcriptional modulation was found during germ layer commitment, emphasizing the translatome potency in capturing nuanced gene expression regulation. These findings highlight the post-transcriptional regulation's critical role in early embryonic development, offering new insights into the molecular mechanisms of cell differentiation.

The tropial genus Beilschmiedia, comprising over 250 species worldwide, includes approximately 40 species distributed in the northern tropical forests of Asia. However, the phylogenetic relationships among these Asiatic Beilschmiedia species remain incompletely understood. In this study, we sequenced and assembled complete chloroplast genomes from six Asiatic Beilschmiedia species, including five from China and one from Indonesia. The genomes range in size from 158,275 to 158,620 bp and exhibit a typical quadripartite structure, similar to other basal Lauraceae species. We identified 116 to 122 simple sequence repeats (SSRs) and 19 to 28 dispersed repeats within the genomes. The relative synonymous codon usage (RSCU) of 79 protein-coding genes exhibited minimal variation. Notably, the boundary genes rpl23 and ycf1 displayed varying degrees of expansion and contraction, along with incomplete replication phenomena. Using a sliding window approach, we constructed a coalescent tree with ASTRAL software to analyze the phylogenetic relationships. The resulting main topology was highly consistent with the Maximum Likelihood (ML) and Bayesian inference (BI) analyses, clearly dividing the Asiatic core Beilschmiedia into two distinct groups: Group A and Group B. Group A showed an extremely low nucleotide diversity (π) value of 0.00063, while Group B exhibited 2.79-fold higher diversity. The highly variable regions trnS-trnG and rpl32-trnL are proposed as molecular markers for distinguishing between Groups A and B. Furthermore, we identified seven additional highly variable regions: ndhF, ndhF-rpl32, rpl2, rpl2-trnH, rpl32, rps15-ycf1, and ycf1. These regions may serve as potential molecular markers for the Asiatic Beilschmiedia species. These findings provide new insights into the phylogenetic relationships among Asiatic Beilschmiedia species, highlighting the potential of specific molecular markers in future research.

Background: QN Orange scallops are interspecific hybrids with orange adductor muscles that are rich in carotenoids. In this study, analysis of miRNA expression profiles was performed to explore possible regulatory patterns involved in carotenoid accumulation in adductor muscles of QN Orange scallops.

Results: A total of 91 differentially expressed miRNA between the white and orange adductor muscles were identified. GO and KEGG analysis of target genes of differentially expressed miRNAs revealed enrichments in the transmembrane transporter activity-related pathways, kinase activity-related pathways, signal transduction-related pathways, ATP binding cassette transporters (ABC transporters), retinol metabolism, lipid-related metabolism, and calcium signaling pathway. In particular, miRNA Contig1462_36180, which was shown to negatively regulate the activity of methyltransferase 3 (METTL3) by dual-luciferase reporter assay, may play a pivotal role in the accumulation of carotenoids. Furthermore, METTL3 interference seemed to reduce the pectenoxanthin content and m6A level.

Conclusion: It is thus speculated that Contig1462_36180 may regulate m6A methylation by regulating METTL3, which in turn affects pectenoxanthin accumulation in QN Orange scallops.

Background: Cotton fiber development relies on complex and intricate biological processes to transform newly differentiated fiber initials into the mature, extravagantly elongated cellulosic cells that are the foundation of this economically important cash crop. Here we extend previous research into cotton fiber development by employing controlled conditions to minimize variability and utilizing time-series sampling and analyses to capture daily transcriptomic changes from early elongation through the early stages of secondary wall synthesis (6 to 24 days post anthesis; DPA).

Results: A majority of genes are expressed in fiber, largely partitioned into two major coexpression modules that represent genes whose expression generally increases or decreases during development. Differential gene expression reveals a massive transcriptomic shift between 16 and 17 DPA, corresponding to the onset of the transition phase that leads to secondary wall synthesis. Subtle gene expression changes are captured by the daily sampling, which are discussed in the context of fiber development. Coexpression and gene regulatory networks are constructed and associated with phenotypic aspects of fiber development, including turgor and cellulose production. Key genes are considered in the broader context of plant secondary wall synthesis, noting their known and putative roles in cotton fiber development.

Conclusions: The analyses presented here highlight the importance of fine-scale temporal sampling on understanding developmental processes and offer insight into genes and regulatory networks that may be important in conferring the unique fiber phenotype.