The bovine alveolar macrophage DNA methylome is resilient to infection with Mycobacterium bovis

Scientific Reports ◽

10.1038/s41598-018-37618-z ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Alan Mark O’Doherty ◽

Kevin Christophe Rue-Albrecht ◽

David Andrew Magee ◽

Simone Ahting ◽

Rachelle Elizabeth Irwin ◽

...

Keyword(s):

Alveolar Macrophage ◽

Mycobacterium Bovis ◽

Dna Methylome ◽

Bovine Alveolar Macrophage

Quantitative modelling predicts the impact of DNA methylation on RNA polymerase II traffic

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1903549116 ◽

2019 ◽

Vol 116 (30) ◽

pp. 14995-15000 ◽

Cited By ~ 13

Author(s):

Justyna Cholewa-Waclaw ◽

Ruth Shah ◽

Shaun Webb ◽

Kashyap Chhatbar ◽

Bernard Ramsahoye ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Rna Polymerase ◽

Rna Polymerase Ii ◽

Rett Syndrome ◽

Transcription Initiation ◽

Expression Patterns ◽

Global Gene Expression ◽

A Genome ◽

The Impact

Patterns of gene expression are primarily determined by proteins that locally enhance or repress transcription. While many transcription factors target a restricted number of genes, others appear to modulate transcription levels globally. An example is MeCP2, an abundant methylated-DNA binding protein that is mutated in the neurological disorder Rett syndrome. Despite much research, the molecular mechanism by which MeCP2 regulates gene expression is not fully resolved. Here, we integrate quantitative, multidimensional experimental analysis and mathematical modeling to indicate that MeCP2 is a global transcriptional regulator whose binding to DNA creates “slow sites” in gene bodies. We hypothesize that waves of slowed-down RNA polymerase II formed behind these sites travel backward and indirectly affect initiation, reminiscent of defect-induced shockwaves in nonequilibrium physics transport models. This mechanism differs from conventional gene-regulation mechanisms, which often involve direct modulation of transcription initiation. Our findings point to a genome-wide function of DNA methylation that may account for the reversibility of Rett syndrome in mice. Moreover, our combined theoretical and experimental approach provides a general method for understanding how global gene-expression patterns are choreographed.

199 IN VITRO-DEVELOPED BOVINE BLASTOCYSTS ARE MARKED WITH ABERRANT HYPER- AND HYPO-METHYLATED GENOMIC REGIONS

Reproduction Fertility and Development ◽

10.1071/rdv27n1ab199 ◽

2015 ◽

Vol 27 (1) ◽

pp. 190

Author(s):

D. Salilew-Wondim ◽

M. Hoelker ◽

U. Besenfelder ◽

V. Havlicek ◽

F. Rings ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Expression Patterns ◽

Proximal Promoter ◽

Altered Gene Expression ◽

Genome Wide ◽

Altered Gene ◽

Genomic Regions

Most often, in vitro produced embryos display poor quality and altered gene expression patterns compared to their in vivo counterparts. Aberrant DNA methylation occurring during in vitro embryo development is believed to be one of the multifaceted factors which may cause altered gene expression and poor embryo quality. Here, we investigated the genome-wide DNA methylation patterns of in vitro derived embryos using the recently developed Bovine EmbryoGENE Methylation Platform (BEGMP) array (Shojaei Saadi et al. BMC Genomics 2014 15, 451. doi: 10.1186/1471-2164-15-451) to unravel the aberrantly methylated genomic region in in vitro developed embryos. For this, in vitro and in vivo produced blastocysts were produced and used for genome-wide DNA methylation analysis. In vitro blastocysts were produced from oocytes retrieved from ovaries collected from the local abattoir and matured, fertilized, and cultured in vitro using SOF media. The in vivo blastocysts were produced by superovulation and AI of Simmental heifers followed by uterine flushing. Genomic DNA (gDNA) was then isolated from four replicates (each 10 blastocysts) of in vivo and in vitro derived blastocysts using Allprep DNA/RNA micro kit (Qiagen, Valencia, CA, USA) and the gDNA was then fragmented using the MseI enzyme. Following this, MseLig21 and MseLig were ligated to the MseI-digested genomic fragments in the presence of Ligase enzyme. Methyl-sensitive enzymes, HpaII, AciI, and Hinp1I, were used to cleave unmethlayted genomic regions within the MseI-MseI region of the fragmented DNA. The gDNA was subjected to two rounds of ligation-mediated polymerase chain reaction (LM-PCR) amplification. After removal of the adapters, the amplified gDNA samples from in vivo or in vitro groups were labelled either Cy-3 or Cy-5 dyes in dye-swap design using ULS Fluorescent gDNA labelling kit (Kreatech Biotechnology BV, Amsterdam, The Netherlands). Hybridization was performed for 40 h at 65°C. Slides were scanned using Agilent's High-Resolution C Scanner (Agilent Technologies Inc., Santa Clara, CA, USA) and features were extracted with Agilent's Feature Extraction software (Agilent Technologies Inc.). The results have shown that from a total of 414 566 probes harboured by the BEGMP array, 248 453 and 253 147 probes were detected in in vitro and in vivo derived blastocysts, respectively. Data analysis using the linear modelling for microarray (LIMMA) package and R software (The R Project for Statistical Computing, Vienna, Austria) revealed a total of 3434 differentially methylated regions (DMRs; Fold change ≥1.5, P-value <0.05), of which 42 and 58% were hyper- and hypo-methylated, respectively, in in vitro derived blastocysts compared to their in vivo counterparts. The DMRs were found to be localised in the intronic, exonic, promoter, proximal promoter, and distal promoter, and some of the probes did not have nearby genes. In addition, 10.8% of the DMRs were found to be stretched in short, long, or intermediate CpG islands. Thus, this study demonstrated genome-wide dysregulation in the epigenome landscape of in vitro-derived embryos by the time they reach to the blastocysts stage.

Global epigenetic and metabolic changes accompany the alterations in fruit size and shape of Cucurbita pepo L. intra-species grafting

10.7287/peerj.preprints.3389v1 ◽

2017 ◽

Author(s):

Aliki Xanthopoulou ◽

Aphrodite Tsaballa ◽

Ioannis Ganopoulos ◽

Aliki Kapazoglou ◽

Evangellia Avramidou ◽

...

Keyword(s):

Dna Methylation ◽

Cucurbita Pepo ◽

Molecular Mechanisms ◽

Expression Patterns ◽

Fruit Size ◽

Fruit Shape ◽

Phenotypic Changes ◽

Size And Shape ◽

Fruit Size And Shape ◽

The Impact

To further understand the impact of grafting on fruit characteristics and to comprehend the mechanisms involved in graft-induced changes we studied homo- and hetero- grafted Cucurbita pepo cultivars (cv.) that vary in fruit size and shape. C. pepo cv. ‘Munchkin’ (small fruit) and cv. ‘Big Moose’ (large fruit) as well as cv. ‘Round green’ (round fruit) and cv. ‘Princess’ (elongated fruit) were homografted and reciprocally heterografted. The results show significant changes in fruit size when ‘Big Moose’ was grafted onto ‘Munchkin’ rootstocks in comparison to homo-grafted controls. Moderate changes in fruit shape were observed when grafting of cv. ‘Round green’ and cv. ‘Princess’ were performed. This is the first report of such phenotypic changes after intra-species/inter-cultivar grafting in Cucurbitaceae. Additionally, we found significant changes in i) secondary metabolite profile, ii) global DNA methylation pattern and iii) miRNA expression patterns in grafted scions and iv) DNA methylation on graft-induced phenotypic changes in grafted plants. Our results contribute to further understanding graft-induced effects on fruit morphology in intra-species grafting. Furthermore, our results pave the way for understanding the role of phenolic metabolites and epigenetic molecular mechanisms on the phenotypic changes recorded.

MicroRNA profiling of the bovine alveolar macrophage response to Mycobacterium bovis infection suggests pathogen survival is enhanced by microRNA regulation of endocytosis and lysosome trafficking

Tuberculosis ◽

10.1016/j.tube.2014.10.011 ◽

2015 ◽

Vol 95 (1) ◽

pp. 60-67 ◽

Cited By ~ 32

Author(s):

Peter Vegh ◽

David A. Magee ◽

Nicolas C. Nalpas ◽

Kenneth Bryan ◽

Matthew S. McCabe ◽

...

Keyword(s):

Alveolar Macrophage ◽

Mycobacterium Bovis ◽

Macrophage Response ◽

Microrna Regulation ◽

Microrna Profiling ◽

Pathogen Survival ◽

Bovine Alveolar Macrophage

Somatic cytochrome c (CYCS) gene expression and promoter-specific DNA methylation in a porcine model of prenatal exposure to maternal dietary protein excess and restriction

British Journal Of Nutrition ◽

10.1017/s0007114511003667 ◽

2011 ◽

Vol 107 (6) ◽

pp. 791-799 ◽

Cited By ~ 13

Author(s):

Simone Altmann ◽

Eduard Murani ◽

Manfred Schwerin ◽

Cornelia C. Metges ◽

Klaus Wimmers ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Porcine Model ◽

Expression Patterns ◽

Methylation Status ◽

Special Focus ◽

Cpg Sites ◽

Low Protein ◽

Protein Supply ◽

The Impact

There is growing evidence that maternal nutrition during gestation has an important effect on offspring development as well as on their gene expression with long-term effects on the metabolic state. A potential mechanism forming long-lasting gene expression patterns is DNA methylation of cytosine in CpG dinucleotides within the promoter region of distinct genes. There has been special focus on mitochondrial dysfunction by prenatal malnourishment over the recent years. To this end, we investigated the gene expression of somatic cytochrome c (CYCS), an important member of the respiratory chain, in a porcine model of gestational protein over- and undersupply at 94 d post-conception and 1, 28 and 188 d of age, and analysed the association with the DNA methylation status within the CYCS promoter. Gene expression on day 1 post natum showed a significant increase in the low protein (LP) group (P = 0·0005) and a slight increase in the high protein (HP) group (P = 0·079) compared with the control (CO) group in the liver. The mean of the methylation level over forty-seven CpG sites from nucleotide (nt) − 417 to − 10 was significantly decreased in the LP (P = 0·007) and HP (P = 0·009) groups compared with that in the CO group. Excess and restricted protein supply during pregnancy led to hypomethylation of a number of CpG sites in the CYCS promoter, including those representing putative transcription factor-binding sites, associated with elevated expression levels. However, the impact of the low-protein gestation diet is more pronounced, indicating that the offspring could better adapt to excess rather than restricted protein supply.

Quantitative modelling predicts the impact of DNA methylation on RNA polymerase II traffic

10.1101/391904 ◽

2018 ◽

Cited By ~ 1

Author(s):

Justyna Cholewa-Waclaw ◽

Ruth Shah ◽

Shaun Webb ◽

Kashyap Chhatbar ◽

Bernard Ramsahoye ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Rna Polymerase ◽

Rna Polymerase Ii ◽

Rett Syndrome ◽

Transcription Initiation ◽

Expression Patterns ◽

Global Gene Expression ◽

A Genome ◽

The Impact

Patterns of gene expression are primarily determined by proteins that locally enhance or repress transcription. While many transcription factors target a restricted number of genes, others appear to modulate transcription levels globally. An example is MeCP2, an abundant methylated-DNA binding protein that is mutated in the neurological disorder Rett Syndrome. Despite much research, the molecular mechanism by which MeCP2 regulates gene expression is not fully resolved. Here we integrate quantitative, multi-dimensional experimental analysis and mathematical modelling to show that MeCP2 is a novel type of global transcriptional regulator whose binding to DNA creates "slow sites" in gene bodies. Waves of slowed-down RNA polymerase II formed behind these sites travel backward and indirectly affect initiation, reminiscent of defect-induced shock waves in non-equilibrium physics transport models. This mechanism differs from conventional gene regulation mechanisms, which often involve direct modulation of transcription initiation. Our findings uncover a genome-wide function of DNA methylation that may account for the reversibility of Rett syndrome in mice. Moreover, our combined theoretical and experimental approach provides a general method for understanding how global gene expression patterns are choreographed.

Global epigenetic and metabolic changes accompany the alterations in fruit size and shape of Cucurbita pepo L. intra-species grafting

10.7287/peerj.preprints.3389 ◽

2017 ◽

Author(s):

Aliki Xanthopoulou ◽

Aphrodite Tsaballa ◽

Ioannis Ganopoulos ◽

Aliki Kapazoglou ◽

Evangellia Avramidou ◽

...

Keyword(s):

Dna Methylation ◽

Cucurbita Pepo ◽

Molecular Mechanisms ◽

Expression Patterns ◽

Fruit Size ◽

Fruit Shape ◽

Phenotypic Changes ◽

Size And Shape ◽

Fruit Size And Shape ◽

The Impact

To further understand the impact of grafting on fruit characteristics and to comprehend the mechanisms involved in graft-induced changes we studied homo- and hetero- grafted Cucurbita pepo cultivars (cv.) that vary in fruit size and shape. C. pepo cv. ‘Munchkin’ (small fruit) and cv. ‘Big Moose’ (large fruit) as well as cv. ‘Round green’ (round fruit) and cv. ‘Princess’ (elongated fruit) were homografted and reciprocally heterografted. The results show significant changes in fruit size when ‘Big Moose’ was grafted onto ‘Munchkin’ rootstocks in comparison to homo-grafted controls. Moderate changes in fruit shape were observed when grafting of cv. ‘Round green’ and cv. ‘Princess’ were performed. This is the first report of such phenotypic changes after intra-species/inter-cultivar grafting in Cucurbitaceae. Additionally, we found significant changes in i) secondary metabolite profile, ii) global DNA methylation pattern and iii) miRNA expression patterns in grafted scions and iv) DNA methylation on graft-induced phenotypic changes in grafted plants. Our results contribute to further understanding graft-induced effects on fruit morphology in intra-species grafting. Furthermore, our results pave the way for understanding the role of phenolic metabolites and epigenetic molecular mechanisms on the phenotypic changes recorded.

The Predominant microRNAs in β-cell Clusters for Insulin Regulation and Diabetic Control

Current Drug Targets ◽

10.2174/1389450121666191230145848 ◽

2020 ◽

Vol 21 (7) ◽

pp. 722-734

Author(s):

Adele Soltani ◽

Arefeh Jafarian ◽

Abdolamir Allameh

Keyword(s):

Mirna Expression ◽

Expression Profiles ◽

Expression Patterns ◽

Diabetic Control ◽

In Vitro Proliferation ◽

Cell Functions ◽

Mirna Expression Profiles ◽

Multiple Processes ◽

The Impact

micro (mi)-RNAs are vital regulators of multiple processes including insulin signaling pathways and glucose metabolism. Pancreatic β-cells function is dependent on some miRNAs and their target mRNA, which together form a complex regulative network. Several miRNAs are known to be directly involved in β-cells functions such as insulin expression and secretion. These small RNAs may also play significant roles in the fate of β-cells such as proliferation, differentiation, survival and apoptosis. Among the miRNAs, miR-7, miR-9, miR-375, miR-130 and miR-124 are of particular interest due to being highly expressed in these cells. Under diabetic conditions, although no specific miRNA profile has been noticed, the expression of some miRNAs and their target mRNAs are altered by posttranscriptional mechanisms, exerting diverse signs in the pathobiology of various diabetic complications. The aim of this review article is to discuss miRNAs involved in the process of stem cells differentiation into β-cells, resulting in enhanced β-cell functions with respect to diabetic disorders. This paper will also look into the impact of miRNA expression patterns on in vitro proliferation and differentiation of β-cells. The efficacy of the computational genomics and biochemical analysis to link the changes in miRNA expression profiles of stem cell-derived β-cells to therapeutically relevant outputs will be discussed as well.

Epigenetic Studies in Psychotherapy: A Systematic Review

Current Psychiatry Research and Reviews ◽

10.2174/2666082216999200622140922 ◽

2020 ◽

Vol 16 (2) ◽

pp. 86-92

Author(s):

Rafael Penadés ◽

Bárbara Arias ◽

Mar Fatjó-Vilas ◽

Laura González-Vallespí ◽

Clemente García-Rizo ◽

...

Keyword(s):

Systematic Review ◽

Dna Methylation ◽

Mental Disorders ◽

Epigenetic Modifications ◽

Symptom Improvement ◽

Epigenetic Changes ◽

Main Hypothesis ◽

Psychological Treatments ◽

Time Period ◽

The Impact

Background: Epigenetic modifications appear to be dynamic and they might be affected by environmental factors. The possibility of influencing these processes through psychotherapy has been suggested. Objective: To analyse the impact of psychotherapy on epigenetics when applied to mental disorders. The main hypothesis is that psychological treatments will produce epigenetic modifications related to the improvement of treated symptoms. Methods: A computerised and systematic search was completed throughout the time period from 1990 to 2019 on the PubMed, ScienceDirect and Scopus databases. Results: In total, 11 studies were selected. The studies were evaluated for the theoretical framework, genes involved, type of psychotherapy and clinical challenges and perspectives. All studies showed detectable changes at the epigenetic level, like DNA methylation changes, associated with symptom improvement after psychotherapy. Conclusion: Methylation profiles could be moderating treatment effects of psychotherapy. Beyond the detected epigenetic changes after psychotherapy, the epigenetic status before the implementation could act as an effective predictor of response.