Novel Insights Into Rheumatoid Arthritis Through Characterization of Concordant Changes in DNA Methylation and Gene Expression in Synovial Biopsies of Patients With Differing Numbers of Swollen Joints

In this study, we sought to characterize synovial tissue obtained from individuals with arthralgia and disease-specific auto-antibodies and patients with established rheumatoid arthritis (RA), by applying an integrative multi-omics approach where we investigated differences at the level of DNA methylation and gene expression in relation to disease pathogenesis. We performed concurrent whole-genome bisulphite sequencing and RNA-Sequencing on synovial tissue obtained from the knee and ankle from 4 auto-antibody positive arthralgia patients and thirteen RA patients. Through multi-omics factor analysis we observed that the latent factor explaining the variance in gene expression and DNA methylation was associated with Swollen Joint Count 66 (SJC66), with patients with SJC66 of 9 or more displaying separation from the rest. Interrogating these observed differences revealed activation of the immune response as well as dysregulation of cell adhesion pathways at the level of both DNA methylation and gene expression. We observed differences for 59 genes in particular at the level of both transcript expression and DNA methylation. Our results highlight the utility of genome-wide multi-omics profiling of synovial samples for improved understanding of changes associated with disease spread in arthralgia and RA patients, and point to novel candidate targets for the treatment of the disease.

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Genome-Wide Bisulphite Sequencing Uncovered the Contribution of DNA Methylation to Rice Short-Term Drought Memory Formation

Journal of Plant Growth Regulation ◽

10.1007/s00344-021-10483-3 ◽

2021 ◽

Author(s):

Shuyan Kou ◽

Qiongyao Gu ◽

Liu Duan ◽

Gaojing Liu ◽

Pingrong Yuan ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Drought Stress ◽

Rice Cultivar ◽

Future Research ◽

World Population ◽

Short Term ◽

Stress Memory ◽

Genome Wide ◽

Bisulphite Sequencing

AbstractRice is the important crop for more than half of the world population. However, drought can have a devastating impact on rice growth and reduce yield drastically. Understanding the response of rice to drought stress is especially important for crop breeding. Previously we found that rice enhanced its tolerance to drought stresses via stress memory mechanisms. Numerous memory genes were identified to play important roles in the process. DNA methylation was reported to mediate tolerance via regulating gene expression and enhances the survival rate of rice encountering drought stress. However, how DNA methylation involved in stress memory is still not clear. In this study, genome-wide bisulphite sequencing at a single base resolution methylome profiling level was performed and analyzed in rice cultivar under recurrent drought stresses and recovery treatments. We found that rice drought stress memory-related differentially methylated regions (DMRs) showed dynamic and distinct patterns. The drought-memory DMRs may regulate Transposable elements and gene expression to cope with short-term repeated drought stresses. Our findings of drought-memory DMRs can explain mechanisms of rice drought stress memory in a new perspective on global methylome details. Using epigenetic markers to breed drought-resistant rice would become a feasible way in the future research.

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Novel Insights into Rheumatoid Arthritis Through Characterisation of Concordant Changes in DNA Methylation and Gene Expression in Synovial Biopsies of Patients with Differing Numbers of Swollen Joints

SSRN Electronic Journal ◽

10.2139/ssrn.3576744 ◽

2020 ◽

Author(s):

Enrico Ferrero ◽

Andrew Li Yim ◽

Klio Maratou ◽

Huw D. Lewis ◽

George Royal ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Gene Expression ◽

Dna Methylation

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A Genome-Wide Integrative Association Study of DNA Methylation and Gene Expression Data and Later Life Cognitive Functioning in Monozygotic Twins

Frontiers in Neuroscience ◽

10.3389/fnins.2020.00233 ◽

2020 ◽

Vol 14 ◽

Cited By ~ 1

Author(s):

Mette Soerensen ◽

Dominika Marzena Hozakowska-Roszkowska ◽

Marianne Nygaard ◽

Martin J. Larsen ◽

Veit Schwämmle ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Cognitive Functioning ◽

Association Study ◽

Gene Expression Data ◽

Monozygotic Twins ◽

Later Life ◽

Expression Data ◽

Genome Wide ◽

A Genome

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Retrotransposable L1 elements expressed in rheumatoid arthritis synovial tissue: Association with genomic DNA hypomethylation and influence on gene expression

Arthritis & Rheumatism ◽

10.1002/1529-0131(200012)43:12<2634::aid-anr3>3.0.co;2-1 ◽

2000 ◽

Vol 43 (12) ◽

pp. 2634-2647 ◽

Cited By ~ 145

Author(s):

Michel Neidhart ◽

Janine Rethage ◽

Stefan Kuchen ◽

Peter Künzler ◽

Robert M. Crowl ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Gene Expression ◽

Synovial Tissue ◽

Genomic Dna ◽

Rheumatoid Arthritis Synovial Tissue ◽

Dna Hypomethylation

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DDR1 methylation is associated with bipolar disorder and the isoform expression and methylation of myelin genes

Epigenomics ◽

10.2217/epi-2021-0006 ◽

2021 ◽

Author(s):

Beatriz Garcia-Ruiz ◽

Manuel Castro de Moura ◽

Gerard Muntané ◽

Lourdes Martorell ◽

Elena Bosch ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Bipolar Disorder ◽

Mrna Expression ◽

Gene Expression Analysis ◽

Mrna Levels ◽

Healthy Controls ◽

Genome Wide ◽

Isoform Expression

Aim: To investigate DDR1 methylation in the brains of bipolar disorder (BD) patients and its association with DDR1 mRNA levels and comethylation with myelin genes. Materials & methods: Genome-wide profiling of DNA methylation (Infinium MethylationEPIC BeadChip) corrected for glial composition and DDR1 gene expression analysis in the occipital cortices of individuals with BD (n = 15) and healthy controls (n = 15) were conducted. Results: DDR1 5-methylcytosine levels were increased and directly associated with DDR1b mRNA expression in the brains of BD patients. We also observed that DDR1 was comethylated with a group of myelin genes. Conclusion: DDR1 is hypermethylated in BD brain tissue and is associated with isoform expression. Additionally, DDR1 comethylation with myelin genes supports the role of this receptor in myelination.

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Abstract 40: Disturbed Flow Alters Genomewide DNA Methylation Patterns, Regulating Endothelial Gene Expression and Atherosclerosis

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.34.suppl_1.40 ◽

2014 ◽

Vol 34 (suppl_1) ◽

Author(s):

Jessilyn Dunn ◽

Haiwei Qiu ◽

Soyeon Kim ◽

Daudi Jjingo ◽

Ryan Hoffman ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Dna Methyltransferase ◽

Methylation Status ◽

Western Diet ◽

Dependent Manner ◽

Gene Promoters ◽

Genome Wide ◽

Methylation Patterns ◽

Endothelial Gene Expression

Atherosclerosis preferentially occurs in arterial regions of disturbed blood flow (d-flow), which alters gene expression, endothelial function, and atherosclerosis. Here, we show that d-flow regulates genome-wide DNA methylation patterns in a DNA methyltransferase (DNMT)-dependent manner. We found that d-flow induced expression of DNMT1, but not DNMT3a or DNMT3b, in mouse arterial endothelium in vivo and in cultured endothelial cells by oscillatory shear (OS) compared to unidirectional laminar shear in vitro. The DNMT inhibitor 5-Aza-2’deoxycytidine (5Aza) or DNMT1 siRNA significantly reduced OS-induced endothelial inflammation. Moreover, 5Aza reduced lesion formation in two atherosclerosis models using ApoE-/- mice (western diet for 3 months and the partial carotid ligation model with western diet for 3 weeks). To identify the 5Aza mechanisms, we conducted two genome-wide studies: reduced representation bisulfite sequencing (RRBS) and transcript microarray using endothelial-enriched gDNA and RNA, respectively, obtained from the partially-ligated left common carotid artery (LCA exposed to d-flow) and the right contralateral control (RCA exposed to s-flow) of mice treated with 5Aza or vehicle. D-flow induced DNA hypermethylation in 421 gene promoters, which was significantly prevented by 5Aza in 335 genes. Systems biological analyses using the RRBS and the transcriptome data revealed 11 mechanosensitive genes whose promoters were hypermethylated by d-flow but rescued by 5Aza treatment. Of those, five genes contain hypermethylated cAMP-response-elements in their promoters, including the transcription factors HoxA5 and Klf3. Their methylation status could serve as a mechanosensitive master switch in endothelial gene expression. Our results demonstrate that d-flow controls epigenomic DNA methylation patterns in a DNMT-dependent manner, which in turn alters endothelial gene expression and induces atherosclerosis.

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Genome-wide variation in DNA methylation linked to developmental stage and chromosomal suppression of recombination in white-throated sparrows

10.1101/2020.07.24.220582 ◽

2020 ◽

Cited By ~ 1

Author(s):

Dan Sun ◽

Thomas S. Layman ◽

Hyeonsoo Jeong ◽

Paramita Chatterjee ◽

Kathleen Grogan ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Chromosome Pair ◽

Dna Methyltransferases ◽

Model Organisms ◽

Phenotypic Traits ◽

Zonotrichia Albicollis ◽

Single Nucleotide ◽

Genome Wide ◽

Nucleotide Resolution

ABSTRACTDNA methylation is known to play critical roles in key biological processes. Most of our knowledge on regulatory impacts of DNA methylation has come from laboratory-bred model organisms, which may not exhibit the full extent of variation found in wild populations. Here, we investigated naturally-occurring variation in DNA methylation in a wild avian species, the white-throated sparrow (Zonotrichia albicollis). This species offers exceptional opportunities for studying the link between genetic differentiation and phenotypic traits because of a non-recombining chromosome pair linked to both plumage and behavioral phenotypes. Using novel single-nucleotide resolution methylation maps and gene expression data, we show that DNA methylation and the expression of DNA methyltransferases are significantly higher in adults than in nestlings. Genes for which DNA methylation varied between nestlings and adults were implicated in development and cell differentiation and were located throughout the genome. In contrast, differential methylation between plumage morphs was localized to the non-recombining chromosome pair. One subset of CpGs on the non-recombining chromosome was extremely hypomethylated and localized to transposable elements. Changes in methylation predicted changes in gene expression for both chromosomes. In summary, we demonstrate changes in genome-wide DNA methylation that are associated with development and with specific functional categories of genes in white-throated sparrows. Moreover, we observe substantial DNA methylation reprogramming associated with the suppression of recombination, with implications for genome integrity and gene expression divergence. These results offer an unprecedented view of ongoing epigenetic reprogramming in a wild population.

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Genome-wide DNA methylation and RNA-seq analyses identify genes and pathways associated with doxorubicin resistance in a canine diffuse large B-cell lymphoma cell line

PLoS ONE ◽

10.1371/journal.pone.0250013 ◽

2021 ◽

Vol 16 (5) ◽

pp. e0250013

Author(s):

Chia-Hsin Hsu ◽

Hirotaka Tomiyasu ◽

Chi-Hsun Liao ◽

Chen-Si Lin

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Rna Seq ◽

Doxorubicin Resistance ◽

Large B Cell Lymphoma ◽

Genome Wide ◽

Large B Cell

Doxorubicin resistance is a major challenge in the successful treatment of canine diffuse large B-cell lymphoma (cDLBCL). In the present study, MethylCap-seq and RNA-seq were performed to characterize the genome-wide DNA methylation and differential gene expression patterns respectively in CLBL-1 8.0, a doxorubicin-resistant cDLBCL cell line, and in CLBL-1 as control, to investigate the underlying mechanisms of doxorubicin resistance in cDLBCL. A total of 20289 hypermethylated differentially methylated regions (DMRs) were detected. Among these, 1339 hypermethylated DMRs were in promoter regions, of which 24 genes showed an inverse correlation between methylation and gene expression. These 24 genes were involved in cell migration, according to gene ontology (GO) analysis. Also, 12855 hypermethylated DMRs were in gene-body regions. Among these, 353 genes showed a positive correlation between methylation and gene expression. Functional analysis of these 353 genes highlighted that TGF-β and lysosome-mediated signal pathways are significantly associated with the drug resistance of CLBL-1. The tumorigenic role of TGF-β signaling pathway in CLBL-1 8.0 was further validated by treating the cells with a TGF-β inhibitor(s) to show the increased chemo-sensitivity and intracellular doxorubicin accumulation, as well as decreased p-glycoprotein expression. In summary, the present study performed an integrative analysis of DNA methylation and gene expression in CLBL-1 8.0 and CLBL-1. The candidate genes and pathways identified in this study hold potential promise for overcoming doxorubicin resistance in cDLBCL.

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