scholarly journals Transcriptome and DNA Methylation Analyses of the Molecular Mechanisms Underlying with Longissimus dorsi Muscles at Different Stages of Development in the Polled Yak

Genes ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 970 ◽  
Author(s):  
Ma ◽  
Jia ◽  
Chu ◽  
Fu ◽  
Lei ◽  
...  

DNA methylation modifications are implicated in many biological processes. As the most common epigenetic mechanism DNA methylation also affects muscle growth and development. The majority of previous studies have focused on different varieties of yak, but little is known about the epigenetic regulation mechanisms in different age groups of animals. The development of muscles in the different stages of yak growth remains unclear. In this study, we selected the longissimus dorsi muscle tissue at three different growth stages of the yak, namely, 90-day-old fetuses (group E), six months old (group M), and three years old (group A). Using RNA-Seq transcriptome sequencing and methyl-RAD whole-genome methylation sequencing technology, changes in gene expression levels and DNA methylation status throughout the genome were investigated during the stages of yak development. Each group was represented by three biological replicates. The intersections of expression patterns of 7694 differentially expressed genes (DEGs) were identified (padj < 0.01, |log2FC| > 1.2) at each of the three developmental periods. Time-series expression profile clustering analysis indicated that the DEGs were significantly arranged into eight clusters which could be divided into two classes (padj < 0.05), class I profiles that were downregulated and class II profiles that were upregulated. Based on this cluster analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that DEGs from class I profiles were significantly (padj < 0.05) enriched in 21 pathways, the most enriched pathway being the Axon guidance signaling pathway. DEGs from the class II profile were significantly enriched in 58 pathways, the pathway most strongly enriched being Metabolic pathway. After establishing the methylation profiles of the whole genomes, and using two groups of comparisons, the three combinations of groups (M-vs.-E, M-vs.-A, A-vs.-E) were found to have 1344, 822, and 420 genes, respectively, that were differentially methylated at CCGG sites and 2282, 3056, and 537 genes, respectively, at CCWGG sites. The two sets of data were integrated and the negative correlations between DEGs and differentially methylated promoters (DMPs) analyzed, which confirmed that TMEM8C, IGF2, CACNA1S and MUSTN1 were methylated in the promoter region and that expression of the modified genes was negatively correlated. Interestingly, these four genes, from what was mentioned above, perform vital roles in yak muscle growth and represent a reference for future genomic and epigenomic studies in muscle development, in addition to enabling marker-assisted selection of growth traits.

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 808
Author(s):  
Chaofan Jin ◽  
Mengya Wang ◽  
Weihao Song ◽  
Xiangfu Kong ◽  
Fengyan Zhang ◽  
...  

Myosins are important eukaryotic motor proteins that bind actin and utilize the energy of ATP hydrolysis to perform a broad range of functions such as muscle contraction, cell migration, cytokinesis, and intracellular trafficking. However, the characterization and function of myosin is poorly studied in teleost fish. In this study, we identified 60 myosin family genes in a marine teleost, black rockfish (Sebastes schlegelii), and further characterized their expression patterns. myosin showed divergent expression patterns in adult tissues, indicating they are involved in different types and compositions of muscle fibers. Among 12 subfamilies, S. schlegelii myo2 subfamily was significantly expanded, which was driven by tandem duplication events. The up-regulation of five representative genes of myo2 in the skeletal muscle during fast-growth stages of juvenile and adult S. schlegelii revealed their active role in skeletal muscle fiber synthesis. Moreover, the expression regulation of myosin during the process of myoblast differentiation in vitro suggested that they contribute to skeletal muscle growth by involvement of both myoblast proliferation and differentiation. Taken together, our work characterized myosin genes systemically and demonstrated their diverse functions in a marine teleost species. This lays foundation for the further studies of muscle growth regulation and molecular mechanisms of indeterminate skeletal muscle growth of large teleost fishes.


Biomolecules ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. 289 ◽  
Author(s):  
Karin Jasek ◽  
Peter Kubatka ◽  
Marek Samec ◽  
Alena Liskova ◽  
Karel Smejkal ◽  
...  

The modulation of the activity of DNA methyltransferases (DNMTs) represents a crucial epigenetic mechanism affecting gene expressions or DNA repair mechanisms in the cells. Aberrant modifications in the function of DNMTs are a fundamental event and part of the pathogenesis of human cancer. Phytochemicals, which are biosynthesized in plants in the form of secondary metabolites, represent an important source of biomolecules with pleiotropic effects and thus provide a wide range of possible clinical applications. It is well documented that phytochemicals demonstrate significant anticancer properties, and in this regard, rapid development within preclinical research is encouraging. Phytochemicals affect several epigenetic molecular mechanisms, including DNA methylation patterns such as the hypermethylation of tumor-suppressor genes and the global hypomethylation of oncogenes, that are specific cellular signs of cancer development and progression. This review will focus on the latest achievements in using plant-derived compounds and plant-based diets targeting epigenetic regulators and modulators of gene transcription in preclinical and clinical research in order to generate novel anticancer drugs as sensitizers for conventional therapy or compounds suitable for the chemoprevention clinical setting in at-risk individuals. In conclusion, indisputable anticancer activities of dietary phytochemicals linked with proper regulation of DNA methylation status have been described. However, precisely designed and well-controlled clinical studies are needed to confirm their beneficial epigenetic effects after long-term consumption in humans.


2020 ◽  
Vol 15 (1) ◽  
pp. 753-762
Author(s):  
Delong Kan ◽  
Di Zhao ◽  
Pengfei Duan

AbstractStudies have shown that abundant and various flavonoids accumulate in chili pepper (Capsicum), but there are few reports on the genes that govern chili pepper flavonoid biosynthesis. Here, we report the comprehensive identification of genes encoding type III polyketide synthase (PKS), an important enzyme catalyzing the generation of flavonoid backbones. In total, 13, 14 and 13 type III PKS genes were identified in each genome of C. annuum, C. chinense and C. baccatum, respectively. The phylogeny topology of Capsicum PKSs is similar to those in other plants, as it showed two classes of genes. Within each class, clades can be further identified. Class II genes likely encode chalcone synthase (CHS) as they are placed together with the Arabidopsis CHS gene, which experienced extensive expansions in the genomes of Capsicum. Interestingly, 8 of the 11 Class II genes form three clusters in the genome of C. annuum, which is likely the result of tandem duplication events. Four genes are not expressed in the tissues of C. annuum, three of which are located in the clusters, indicating that a portion of genes was pseudogenized after tandem duplications. Expression of two Class I genes was complementary to each other, and all the genes in Class II were not expressed in roots of C. annuum. Two Class II genes (CA00g90790 and CA05g17060) showed upregulated expression as the chili pepper leaves matured, and two Class II genes (CA05g17060 and CA12g20070) showed downregulated expression with the maturation of fruits, consistent with flavonoid accumulation trends in chili pepper as reported previously. The identified genes, sequences, phylogeny and expression information collected in this article lay the groundwork for future studies on the molecular mechanisms of chili pepper flavonoid metabolism.


2017 ◽  
Author(s):  
Yong Li ◽  
Yi Jin Liew ◽  
Guoxin Cui ◽  
Maha J Cziesielski ◽  
Noura Zahran ◽  
...  

The symbiotic relationship between cnidarians and dinoflagellates is the cornerstone of coral reef ecosystems. Although research is focusing on the molecular mechanisms underlying this symbiosis, the role of epigenetic mechanisms, which have been implicated in transcriptional regulation and acclimation to environmental change, is unknown. To assess the role of DNA methylation in the cnidarian-dinoflagellate symbiosis, we analyzed genome-wide CpG methylation, histone associations, and transcriptomic states of symbiotic and aposymbiotic anemones in the model systemAiptasia. We find methylated genes are marked by histone H3K36me3 and show significant reduction of spurious transcription and transcriptional noise, revealing a role of DNA methylation in the maintenance of transcriptional homeostasis. Changes in DNA methylation and expression show enrichment for symbiosis-related processes such as immunity, apoptosis, phagocytosis recognition and phagosome formation, and unveil intricate interactions between the underlying pathways. Our results demonstrate that DNA methylation provides an epigenetic mechanism of transcriptional homeostasis during symbiosis.


Epigenomics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 747-755
Author(s):  
Veronika Suni ◽  
Fatemeh Seyednasrollah ◽  
Bishwa Ghimire ◽  
Sini Junttila ◽  
Asta Laiho ◽  
...  

Aim: DNA methylation is a key epigenetic mechanism regulating gene expression. Identifying differentially methylated regions is integral to DNA methylation analysis and there is a need for robust tools reliably detecting regions with significant differences in their methylation status. Materials & methods: We present here a reproducibility-optimized test statistic (ROTS) for detection of differential DNA methylation from high-throughput sequencing or array-based data. Results: Using both simulated and real data, we demonstrate the ability of ROTS to identify differential methylation between sample groups. Conclusion: Compared with state-of-the-art methods, ROTS shows competitive sensitivity and specificity in detecting consistently differentially methylated regions.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4386-4386
Author(s):  
Ye Zhao ◽  
Zi-xing Chen ◽  
Shao-yan Hu ◽  
Jian-nong Cen

Abstract The methylation at CpG island in the promoter region of a gene is one of the important epigenetic mechanism which regulates the gene activity. To study the DNA methylation pattern of WT1 gene promoter region within hematologic neoplastic cell lines and its correlation with WT1 gene expression by using the PCR-based methods. RT-PCR and Methylation-specific PCR were performed to study the WT1 gene expression in 8226, HL-60, Jurkat, K562, KG-1, NB4, Raji, SHI-1, U266 and U937 cell lines and the DNA methylation status in promoter region of WT1 gene. After treatment of U937 cell line by 5-aza-CdR, a demethylation inducing agent, the changes of WT1 gene expression level and the methylation status in its promter region in U937 cells was determined. Our Results showed that HL-60, K562, KG-1, NB4, SHI-1 cell lines demonstrated higher level of WT1 expression, while extremely low level was found in 8226, Jurkat, Raji, U266 and U937. The DNA hypermethylation in WT1 gene promoter region was identified in 8226, Jurkat, Raji, U266 and U937 cell lines. The WT1 gene expression in U937 was markedly enhanced after treatment with 5-aza-CdR in company with the decrease of methylated level and the increase of unmethylated level in its promoter region. These results indicate that modulation of the DNA methylation in WT1 promoter region is one of the epigenetic mechanisms to regulate its expression.


2015 ◽  
Vol 308 (10) ◽  
pp. E912-E920 ◽  
Author(s):  
Timo Kanzleiter ◽  
Markus Jähnert ◽  
Gunnar Schulze ◽  
Joachim Selbig ◽  
Nicole Hallahan ◽  
...  

The adaptive response of skeletal muscle to exercise training is tightly controlled and therefore requires transcriptional regulation. DNA methylation is an epigenetic mechanism known to modulate gene expression, but its contribution to exercise-induced adaptations in skeletal muscle is not well studied. Here, we describe a genome-wide analysis of DNA methylation in muscle of trained mice ( n = 3). Compared with sedentary controls, 2,762 genes exhibited differentially methylated CpGs ( P < 0.05, meth diff >5%, coverage >10) in their putative promoter regions. Alignment with gene expression data ( n = 6) revealed 200 genes with a negative correlation between methylation and expression changes in response to exercise training. The majority of these genes were related to muscle growth and differentiation, and a minor fraction involved in metabolic regulation. Among the candidates were genes that regulate the expression of myogenic regulatory factors ( Plexin A2) as well as genes that participate in muscle hypertrophy ( Igfbp4) and motor neuron innervation ( Dok7). Interestingly, a transcription factor binding site enrichment study discovered significantly enriched occurrence of CpG methylation in the binding sites of the myogenic regulatory factors MyoD and myogenin. These findings suggest that DNA methylation is involved in the regulation of muscle adaptation to regular exercise training.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 364-364
Author(s):  
Nicola Cahill ◽  
Meena Kanduri ◽  
Hanna Göransson ◽  
Anders Isaksson ◽  
Camilla Enström ◽  
...  

Abstract Abstract 364 Introduction: Aberrant DNA methylation has been shown to play a strong role in tumorogenesis, where genome-wide hypomethylation and regional hypermethylation of tumor suppressor gene (TGS) promoters are characteristic hallmarks of many cancers. In chronic lymphocytic leukemia (CLL), the epigenetic mechanism of gene regulation has thus far received limited attention, although promoter methylation and transcriptional silencing has been shown for certain individual genes, for example, DAPK1, ZAP70 and PEG10. To date, only the ‘Restriction Landmark Genomic Scanning' technique has been performed to assess the genome-wide methylation status in CLL. However, this technique spans only 3000 CpG islands and does not give a full coverage of the genome. Patients and methods: Here, we analyzed the global methylation profiles in CLL by applying high-resolution genome-wide methylation arrays from Illumina that cover 28,000 CpG sites, spanning 14,000 genes. Specifically, 23 CLL samples belonging to the immunoglobulin heavy-chain variable (IGHV) mutated (favorable prognostic) and IGHV unmutated/IGHV3-21 (poor-prognostic) subsets were analysed. The raw data was processed using the BeadStudio software followed by bioinformatic analysis where the arcsin transformed data was used in a moderated t-test to find differentially methylated genes. Only genes with a large absolute difference between the groups were included for further analysis. Methylation-specific PCR (MSP-PCR) and realtime-PCR (RQ-PCR) were performed on a selection of genes to confirm the array data. Additionally, bi-sulfite sequencing was employed on selected genes to confirm the degree of methylation. Moreover, CLL samples were treated with the DNA methyl transferase inhibitor 5-aza-2'-deoxycytidine combined with and without the histone deacetylase inhibitor (HDAC) trichostatin A to induce re-expression of selected methylated genes Results: Overall, we observed significant differences in methylation patterns between the CLL subgroups. Specifically, we identified TSGs that were preferentially methylated in the IGHV unmutated (7 genes, e.g. VHL, ABI3) and IGHV3-21(1 gene, SLC22A18) subgroups. We also identified 10 unmethylated and hence potentially expressed genes shown to be involved in activation of proliferative pathways such as the NFkB pathway (e.g. ADORA3), and the MAP/ERK kinase pathway (e.g. FABP7) in the IGHV unmutated and IGHV3-21 subgroups. In contrast, these latter genes were silenced by methylation in IGHV mutated patients. The methylation status was verified for 4 genes (BCL10, PRF1, ADORA3 and IGSF4) by MSP-PCR and the expression status of 7 genes (BCL10, PRF1, ADORA3, IGSF4, NGFR, ABI3 and VHL) was confirmed using RQ-PCR. Furthermore, bi-sulfite sequencing confirmed the degree of methylation for 2 methylated TSGs (VHL and ABI3) in unmutated CLL samples. Finally, the significance of DNA methylation in regulating gene promoters was shown by re-inducing 3 methylated TSGs ( VHL, ABI3 and IGSF4) in IGHV unmutated samples using the methyl-inhibitor 5-aza-2'-deoxycytidine. Conclusion: Taken together, our data for the first time reveals differences in global methylation profiles between prognostic subsets of CLL, which may unfold important epigenetic silencing mechanisms involved in CLL pathogenesis. Specific inhibition of expression of unmethylated genes involved in facilitating tumorogenesis and re-expression of methylated tumor suppressor genes within the poor-prognostic CLL subgroups may represent potential new drug therapy targets. Disclosures: No relevant conflicts of interest to declare.


2006 ◽  
Vol 17 (9) ◽  
pp. 3729-3744 ◽  
Author(s):  
Roy M. Katso ◽  
Olivier E. Pardo ◽  
Andrea Palamidessi ◽  
Clemens M. Franz ◽  
Marin Marinov ◽  
...  

Receptor-linked class I phosphoinositide 3-kinases (PI3Ks) induce assembly of signal transduction complexes through protein–protein and protein–lipid interactions that mediate cell proliferation, survival, and migration. Although class II PI3Ks have the potential to make the same phosphoinositides as class I PI3Ks, their precise cellular role is currently unclear. In this report, we demonstrate that class II phosphoinositide 3-kinase C2β (PI3KC2β) associates with the Eps8/Abi1/Sos1 complex and is recruited to the EGF receptor as part of a multiprotein signaling complex also involving Shc and Grb2. Increased expression of PI3KC2β stimulated Rac activity in A-431 epidermoid carcinoma cells, resulting in enhanced membrane ruffling and migration speed of the cells. Conversely, expression of dominant negative PI3KC2β reduced Rac activity, membrane ruffling, and cell migration. Moreover, PI3KC2β-overexpressing cells were protected from anoikis and displayed enhanced proliferation, independently of Rac function. Taken together, these findings suggest that PI3KC2β regulates the migration and survival of human tumor cells by distinct molecular mechanisms.


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