scholarly journals Comparative methylation and RNA-seq expression analysis in CpG context to identify genes involved in Backfat vs. Liver diversification in Nanchukmacdon Pig

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Devender Arora ◽  
Jong-Eun Park ◽  
Dajeong Lim ◽  
Bong-Hwan Choi ◽  
In-Cheol Cho ◽  
...  
Keyword(s):  
Cholesterol Biosynthesis ◽  
Critical Role ◽  
Cpg Islands ◽  
Bmp Signaling ◽  
Salt Transport ◽  
Rna Seq ◽  
Motif Analysis ◽  
Tissue Samples ◽  
Tissue Specific

Abstract Background DNA methylation and demethylation at CpG islands is one of the main regulatory factors that allow cells to respond to different stimuli. These regulatory mechanisms help in developing tissue without affecting the genomic composition or undergoing selection. Liver and backfat play important roles in regulating lipid metabolism and control various pathways involved in reproductive performance, meat quality, and immunity. Genes inside these tissue store a plethora of information and an understanding of these genes is required to enhance tissue characteristics in the future generation. Results A total of 16 CpG islands were identified, and they were involved in differentially methylation regions (DMRs) as well as differentially expressed genes (DEGs) of liver and backfat tissue samples. The genes C7orf50, ACTB and MLC1 in backfat and TNNT3, SIX2, SDK1, CLSTN3, LTBP4, CFAP74, SLC22A23, FOXC1, GMDS, GSC, GATA4, SEMA5A and HOXA5 in the liver, were categorized as differentially-methylated. Subsequently, Motif analysis for DMRs was performed to understand the role of the methylated motif for tissue-specific differentiation. Gene ontology studies revealed association with collagen fibril organization, the Bone Morphogenetic Proteins (BMP) signaling pathway in backfat and cholesterol biosynthesis, bile acid and bile salt transport, and immunity-related pathways in methylated genes expressed in the liver. Conclusions In this study, to understand the role of genes in the differentiation process, we have performed whole-genome bisulfite sequencing (WGBS) and RNA-seq analysis of Nanchukmacdon pigs. Methylation and motif analysis reveals the critical role of CpG islands and transcriptional factors binding site (TFBS) in guiding the differential patterns. Our findings could help in understanding how methylation of certain genes plays an important role and can be used as biomarkers to study tissue specific characteristics.

scholarly journals Comparative Methylation and RNA-Seq Expression Analysis in CpG Context to Identify Genes Involved in Backfat vs Liver Diversification in Nanchukmacdon Pig

2021 ◽  
Author(s):  
Devender Arora ◽  
Jong-Eun Park ◽  
Dajeong Lim ◽  
Bong-Hwan Choi ◽  
In-Cheol Cho ◽  
...  
Keyword(s):  
Cpg Island ◽  
Cholesterol Biosynthesis ◽  
Bmp Signaling ◽  
Salt Transport ◽  
Regulatory Mechanisms ◽  
Transcriptional Level ◽  
Rna Seq ◽  
Motif Analysis ◽  
Tissue Specific ◽  
Differentially Methylated Genes

Abstract Background: DNA methylation and demethylation at CpG island is one of the main regulatory mechanisms at the transcriptional level that give cells the possibility to respond to different stimuli. These regulatory mechanisms help in developing tissue without affecting the genomic composition or undergone selection. Liver and Backfat play important role in regulating lipid metabolism and control various pathways involved in reproductive performance, meat quality, and immunity. Genes inside these tissue stores plethora of information and their understanding are required to enhance tissue characteristics in the future generation. Results: In this study, to understand the differentiation mechanism we have performed whole-genome bisulfite sequencing (WGBS) and RNA-seq analysis and identified 16 CpG islands were involved in differentially methylation regions (DMRs) as well differentially expressed genes (DEGs) between liver and backfat. Among the identified differentially-methylated genes (C7orf50, ACTB, MLC1) in backfat and (TNNT3, SIX2, SDK1, CLSTN3, LTBP4, CFAP74, SLC22A23, FOXC1, GMDS, GSC, GATA4, SEMA5A, HOXA5) in the liver were identified. Motif analysis for DMRs was also performed to understand the major role of methylated motif for tissue-specific differentiation. Gene ontology studies revealed the association with collagen fibril organization, BMP signaling pathway in backfat and Cholesterol biosynthesis, bile acid and bile salt transport, immunity-related pathways in methylated genes expressed in the liver. Conclusion: Our finding could help in understanding how methylation on certain genes plays an important role and can be used as biomarkers to study tissue specific characteristics.

scholarly journals p38β - MAPK11 and its role in female cancers

2020 ◽  
Author(s):  
Periklis Katopodis ◽  
Rachel Kerslake ◽  
Athanasios Zikopoulos ◽  
Nefeli Eirini Beri ◽  
Vladimir Anikin
Keyword(s):  
Cpg Island ◽  
Methylation Status ◽  
Cpg Islands ◽  
Her2 Status ◽  
Tissue Specific ◽  
Cancer Data ◽  
Signalling Molecules ◽  
Significant Difference

Abstract Background The p38MAPK family of Mitogen Activated Protein Kinases are a group of signalling molecules involved in cell growth, survival, proliferation and differentiation. The widely studied p38α isoform is ubiquitously expressed and is implicated in a number of cancer pathologies, as are p38γ and p38δ. However, the mechanistic role of the isoform, p38β, remains fairly elusive. Recent studies suggest a possible role of p38β in both breast and endometrial cancer with research suggesting involvement in bone metastasis and cancer cell survival. Female tissue specific cancers such as breast, endometrial, uterine and ovary account for over 3,000,000 cancer related incidents annually; advancements in therapeutics and treatment however require a deeper understanding of the molecular aetiology associated with these diseases. This study provides an overview of the MAPK signalling molecule p38β (MAPK11) in female cancers using an in-silico approach. Methods A detailed gene expression and methylation analysis was performed using datasets from cBioportal, CanSar and MEXPRESS. Breast, Uterine Endometrial, Cervical, Ovarian and Uterine Carcinosarcoma TCGA cancer datasets were used and analysed.Results Data using cBioportal and CanSAR suggest that expression of p38β is lower in cancers: BRCA, UCEC, UCS, CESC and OV compared to normal tissue. Methylation data from SMART and MEXPRESS indicate significant probe level variation of CpG island methylation status of the gene MAPK11. Analysis of the genes’ two CpG islands shows that the gene was hypermethylated in the CpG1 with increased methylation seen in BRCA, CESC and UCEC cancer data sets with a slight increase of expression recorded in cancer samples. CpG2 exhibited hypomethylation with no significant difference between samples and high levels of expression. Further analysis from MEXPRESS revealed no significance between probe methylation and altered levels of expression. In addition, no difference in the expression of BRCA oestrogen/progesterone/HER2 status was seen. Conclusion This data provides an overview of the expression of p38β in female tissue specific cancers, showing a decrease in expression of the gene in BRCA, UCEC, CESC, UCS and OV, increasing the understanding of p38β MAPK expression and offering insight for future in-vitro investigation and therapeutic application.

scholarly journals Haemocytes are critical for Drosophila melanogaster post-embryonic development, independent of control of the microbiota

2021 ◽  
Author(s):  
Holly N Stephenson ◽  
Robert Streeck ◽  
Alf Herzig
Keyword(s):  
Embryonic Development ◽  
Adult Development ◽  
Critical Role ◽  
Rna Seq ◽  
Genetic Rescue ◽  
Germ Free ◽  
Drosophila Model ◽  
Axenic Conditions ◽  
Driver Line

Proven roles for haemocytes (blood cells) have expanded beyond the control of infections in Drosophila. Despite this, the critical role of haemocytes in post-embryonic development has long been thought to be limited to control of microorganisms during metamorphosis. This has previously been shown by rescue of adult development in haemocyte-ablation models under germ-free conditions. Here we show that haemocytes have a critical role in post-embryonic development beyond their ability to control the microbiota. Using a newly generated, strong haemocyte-specific driver line for the GAL4/UAS system, we show that specific ablation of haemocytes is pupal lethal, even under axenic conditions. Genetic rescue experiments prove that this is a haemocyte-specific phenomena. RNA-seq data suggests that dysregulation of the midgut is a critical consequence of haemocyte ablation. We believe this novel role of haemocytes during metamorphosis is a major finding for the field. This is an exciting new Drosophila model to study the precise mechanisms in which haemocytes regulate tissue development, findings from which could have far reaching implications beyond invertebrate biology.

Vitamin D3 potentiates the nephroprotective effects of metformin in a rat model of metabolic syndrome: Role of AMPK/SIRT1 activation and DPP-4 inhibition

2020 ◽  
Author(s):  
Nehal S. Wahba ◽  
Salah A. Ghareib ◽  
Rasha Hassan Abdelghany ◽  
Mohamed Abdel-Aal ◽  
Amira E. Alsemeh
Keyword(s):  
Vitamin D3 ◽  
Rat Model ◽  
Serum Lipid ◽  
Molecular Mechanisms ◽  
Therapeutic Agent ◽  
Interstitial Fibrosis ◽  
Synergistic Effects ◽  
Critical Role ◽  
Tissue Samples

The current study aimed to investigate the molecular mechanisms of metformin and vitamin D3-induced nephroprotection in a MetS rat model, evaluating the capacity of vitamin D3 to potentiate metformin action. MetS was induced by 10% fructose in drinking water and 3% salt of the diet. After 6 weeks, serum lipid profile and uric acid were measured, an OGTT was performed and kidney function was investigated. MetS rats with significant weight gain, dyslipidemia, hyperuricemia and dysglycemia were treated orally with metformin (200 mg/kg), vitamin D3 (10 µg/kg) or both daily for 6 weeks. At the end of the study period, anthropometrical parameters were recorded, OGTT was reperformed, urine and blood samples were collected and tissue samples were harvested at sacrifice. MetS rats showed dramatically declined renal function, enhanced intrarenal oxidative stress and inflammation and extravagant renal histopathological damages with interstitial fibrosis. Metformin and vitamin D3 significantly reversed all the aforementioned deleterious effects in MetS rats. The study has verified the nephroprotective effects of metformin and vitamin D3 in MetS, accentuating the critical role of AMPK/SIRT1 activation and DPP-4 inhibition. Given the synergistic effects of the combination, vitamin D3 is worth being investigated as an additional therapeutic agent for preventing MetS-induced nephropathy.

scholarly journals Redundant Role of Tissue-Selective TAFII105 in B Lymphocytes

2002 ◽  
Vol 22 (18) ◽  
pp. 6564-6572 ◽  
Author(s):  
Richard N. Freiman ◽  
Shane R. Albright ◽  
Leslie E. Chu ◽  
Shuang Zheng ◽  
Hong-Erh Liang ◽  
...  
Keyword(s):  
B Cells ◽  
Rna Polymerase Ii ◽  
B Lymphocyte ◽  
Critical Role ◽  
Central Component ◽  
Related Factors ◽  
Tissue Specific ◽  
Regulated Gene Expression

ABSTRACT Regulated gene expression is a complex process achieved through the function of multiple protein factors acting in concert at a given promoter. The transcription factor TFIID is a central component of the machinery regulating mRNA synthesis by RNA polymerase II. This large multiprotein complex is composed of the TATA box binding protein (TBP) and several TBP-associated factors (TAFIIs). The recent discovery of multiple TBP-related factors and tissue-specific TAFIIs suggests the existence of specialized TFIID complexes that likely play a critical role in regulating transcription in a gene- and tissue-specific manner. The tissue-selective factor TAFII105 was originally identified as a component of TFIID derived from a human B-cell line. In this report we demonstrate the specific induction of TAFII105 in cultured B cells in response to bacterial lipopolysaccharide (LPS). To examine the in vivo role of TAFII105, we have generated TAFII105-null mice by homologous recombination. Here we show that B-lymphocyte development is largely unaffected by the absence of TAFII105. TAFII105-null B cells can proliferate in response to LPS, produce relatively normal levels of resting antibodies, and can mount an immune response by producing antigen-specific antibodies in response to immunization. Taken together, we conclude that the function of TAFII105 in B cells is likely redundant with the function of other TAFII105-related cellular proteins.

scholarly journals ADAMTSL4, a Secreted Glycoprotein, Is a Novel Immune-Related Biomarker for Primary Glioblastoma Multiforme

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Zheng Zhao ◽  
Ke-Nan Zhang ◽  
Rui-Chao Chai ◽  
Kuan-Yu Wang ◽  
Ruo-Yu Huang ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Critical Role ◽  
The Body ◽  
Rna Seq ◽  
Clinicopathologic Characteristics ◽  
Who Grade ◽  
Primary Glioblastoma ◽  
Potential Marker ◽  
Independent Indicator

Background. Researches on immunotherapy of glioblastoma multiforme (GBM, WHO grade IV) have increased exponentially in recent years. As a targeted therapy, a series of biomarkers have been identified in local tumor tissue, while circulating marker which could be detected in the body fluids is still lacking. ADAMTSL4, a secreted glycoprotein, was earlier found to play a critical role in a prognostic signature for primary GBM (pGBM). We aimed to investigate the role of ADAMTSL4 at transcriptome level and its relationship with clinical practice in pGBM. Methods. A cohort of 88 pGBM patients with RNA-seq data from the Chinese Glioma Genome Atlas (CGGA) was analyzed, and 168 pGBM patients from TCGA were included as validation. Several bioinformatic methods and predictive tools were applied to investigate the ADAMTSL4-associated immune microenvironment status. Results. We found that ADAMTSL4 was enriched in GBM (WHO grade IV), especially for those with IDH1/2 wild-type and MGMT unmethylated groups. According to the TCGA classification scheme, ADAMTSL4 can act as a potential marker for subtypes with poorer prognosis. Bioinformatic analyses revealed that ADAMTSL4 was significantly correlated to the immune-related processes in GBM (WHO grade IV), especially representing the infiltration of immune cells and complicated tumor microenvironment. Clinically, high expression of ADAMTSL4 was an independent indicator for poor prognosis. Conclusion. The expression of ADAMTSL4 is closely related to the clinicopathologic characteristics of pGBM. Meanwhile, it may play a critical role in immune-related processes. As a secreted glycoprotein, ADAMTSL4 is a promising circulating biomarker for pGBM, deserving further investigations.

scholarly journals Key role of SMN/SYNCRIP and RNA-Motif 7 in spinal muscular atrophy: RNA-Seq and motif analysis of human motor neurons

Brain ◽  
2019 ◽  
Vol 142 (2) ◽  
pp. 276-294 ◽  
Author(s):  
Federica Rizzo ◽  
Monica Nizzardo ◽  
Shikha Vashisht ◽  
Erika Molteni ◽  
Valentina Melzi ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Motor Neurons ◽  
Muscular Atrophy ◽  
Rna Seq ◽  
Motif Analysis ◽  
Human Motor ◽  
Rna Motif

scholarly journals TMEM165 a new player in proteoglycan synthesis: loss of TMEM165 impairs elongation of chondroitin- and heparan-sulfate glycosaminoglycan chains of proteoglycans and triggers early chondrocyte differentiation and hypertrophy

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Sajida Khan ◽  
Malak Sbeity ◽  
François Foulquier ◽  
Lydia Barré ◽  
Mohamed Ouzzine
Keyword(s):  
Heparan Sulfate ◽  
Therapeutic Strategy ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Bmp Signaling ◽  
Proteoglycan Synthesis ◽  
Fibroblast Cells ◽  
Chondrocyte Maturation ◽  
Elongation Process

AbstractTMEM165 deficiency leads to skeletal disorder characterized by major skeletal dysplasia and pronounced dwarfism. However, the molecular mechanisms involved have not been fully understood. Here, we uncover that TMEM165 deficiency impairs the synthesis of proteoglycans by producing a blockage in the elongation of chondroitin-and heparan-sulfate glycosaminoglycan chains leading to the synthesis of proteoglycans with shorter glycosaminoglycan chains. We demonstrated that the blockage in elongation of glycosaminoglycan chains is not due to defect in the Golgi elongating enzymes but rather to availability of the co-factor Mn2+. Supplementation of cell with Mn2+ rescue the elongation process, confirming a role of TMEM165 in Mn2+ Golgi homeostasis. Additionally, we showed that TMEM165 deficiency functionally impairs TGFβ and BMP signaling pathways in chondrocytes and in fibroblast cells of TMEM165 deficient patients. Finally, we found that loss of TMEM165 impairs chondrogenic differentiation by accelerating the timing of Ihh expression and promoting early chondrocyte maturation and hypertrophy. Collectively, our results indicate that TMEM165 plays an important role in proteoglycan synthesis and underline the critical role of glycosaminoglycan chains structure in the regulation of chondrogenesis. Our data also suggest that Mn2+ supplementation may be a promising therapeutic strategy in the treatment of TMEM165 deficient patients.

scholarly journals Genome-Wide Perturbations of Alu Expression and Alu-Associated Post-Transcriptional Regulations Find a Uniqueness in Oligodendroglioma

2021 ◽  
Author(s):  
Taeyoung Hwang ◽  
Sojin Kim ◽  
Tamrin Chowdhury ◽  
Hyeon Jong Yu ◽  
Kyung-Min Kim ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Regulatory Element ◽  
Circular Rna ◽  
Circular Rnas ◽  
Global Changes ◽  
Rna Seq ◽  
Tissue Samples ◽  
Genome Wide ◽  
A Genome

Abstract BackgroundAlu is a primate-specific repeat element in the human genome and has been increasingly appreciated as a regulatory element in many biological processes. But the role of Alu has not been studied comprehensively in brain tumor because an evolutionary perspective has been the subject of little research in brain tumor. We aim to investigate the relevance of Alu to the gliomagenesis.MethodsUsing a total of 41 pairs of neurotypicial brain tissue samples and samples of diverse gliomas, we performed strand-specific RNA-seq and analyzed two Alu-associated post-transcriptional regulations, A-to-I editing and circular RNAs, and Alu expression in a genome-wide way. ResultsWe found that while both A-to-I editing and circular RNA are decreased overall in gliomas, grade 2 oligodendrogliomas do not show this same pattern of global changes. Instead, in comparison with other gliomas, oligodendrogliomas showed a higher proportion of perturbed Alu RNA. Adenosine deaminase acting on RNA 2 (ADAR2) was down-regulated in gliomas other than grade 2 oligodendrogliomas, contributing to the observed Alu-associated perturbation. ConclusionsOur results demonstrate that Alu is associated with glioma development and grade 2 oligodendroglioma exhibits a unique pattern of Alu-associated post-transcriptional regulations, which provides an insight to gliomagenesis from the perspective of an evolutionary genetic element.

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