scholarly journals Methylation and Gene Expression Differences Between Reproductive Castes of Bumblebee Workers

2019 ◽  
Author(s):  
Hollie Marshall ◽  
Zoë N. Lonsdale ◽  
Eamonn B. Mallon
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Social Insects ◽  
Social Insect ◽  
Bombus Terrestris ◽  
Epigenetic Mechanisms ◽  
Biological Processes ◽  
Caste Determination ◽  
Differentially Methylated Genes

AbstractPhenotypic plasticity is the production of multiple phenotypes from a single genome and is notably observed in social insects. Multiple epigenetic mechanisms have been associated with social insect plasticity, with DNA methylation being explored to the greatest extent. DNA methylation is thought to play a role in caste determination in Apis mellifera, and other social insects, but there is limited knowledge on it’s role in other bee species. In this study we analysed whole genome bisulfite sequencing and RNA-seq data sets from head tissue of reproductive and sterile castes of the eusocial bumblebee Bombus terrestris. We found genome-wide methylation in B. terrestris is similar to other social insects and does not differ between reproductive castes. We did, however, find differentially methylated genes between castes, which are enriched for multiple biological processes including reproduction. However we found no relationship between differential methylation and differential gene expression or differential exon usage between castes. Our results also indicate high inter-colony variation in methylation. These findings suggest methylation is associated with caste differences but may serve an alternate function, other than direct caste determination in this species. This study provides the first insights into the nature of a bumblebee caste specific methylome as well as it’s interaction with gene expression and caste specific alternative splicing, providing greater understanding of the role of methylation in phenotypic plasticity within social bee species. Future experimental work is needed to determine the function of methylation and other epigenetic mechanisms in social insects.Impact SummarySocial insects, such as ants, termites, bees and wasps, can produce individuals with extreme physical and behavioural differences within the same colony known as castes (e.g. workers/soldiers/queens). These individuals have similar genomes and many studies have associated epigenetic mechanisms with the differences observed. Epigenetic modifications are changes that affect how genes are expressed without changing the underlying DNA code. Here we investigated differences in DNA methylation (a well researched modified base) between different reproductive castes of the bumblebee, Bombus terrestris, an economically and environmentally important pollinator species. We found B. terrestris has a similar methylation profile to other social insect species in terms of the distribution of methylation throughout the genome and the relationship between methylation and gene expression. Genes that have differences in methylation between reproductive castes are involved in multiple biological processes, including reproduction, suggesting methylation may hold multiple functions in this species. These differentially methylated genes are also different to differentially methylated genes identified between honeybee reproductive castes, again suggesting methylation may have a variable function. These findings provide greater understanding of the role of methylation in caste determination in social insect species.

scholarly journals DNA Methylation Signatures of Bone Metabolism in Osteoporosis and Osteoarthritis Aging-Related Diseases: An Updated Review

2021 ◽  
Vol 22 (8) ◽  
pp. 4244
Author(s):  
Virginia Veronica Visconti ◽  
Ida Cariati ◽  
Simona Fittipaldi ◽  
Riccardo Iundusi ◽  
Elena Gasbarra ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Late Onset ◽  
Bone Diseases ◽  
Epigenetic Mechanisms ◽  
Crucial Point ◽  
Pathological Conditions ◽  
New Findings ◽  
Late Onset Disorders

DNA methylation is one of the most studied epigenetic mechanisms that play a pivotal role in regulating gene expression. The epigenetic component is strongly involved in aging-bone diseases, such as osteoporosis and osteoarthritis. Both are complex multi-factorial late-onset disorders that represent a globally widespread health problem, highlighting a crucial point of investigations in many scientific studies. In recent years, new findings on the role of DNA methylation in the pathogenesis of aging-bone diseases have emerged. The aim of this systematic review is to update knowledge in the field of DNA methylation associated with osteoporosis and osteoarthritis, focusing on the specific tissues involved in both pathological conditions.

scholarly journals The Role of Epigenetic Factors in Psoriasis

2021 ◽  
Vol 22 (17) ◽  
pp. 9294
Author(s):  
Klaudia Dopytalska ◽  
Piotr Ciechanowicz ◽  
Kacper Wiszniewski ◽  
Elżbieta Szymańska ◽  
Irena Walecka
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Significant Role ◽  
Disease Onset ◽  
Epigenetic Mechanisms ◽  
Epigenetic Factors ◽  
Individual Gene ◽  
Immune Mediated ◽  
Non Coding Rnas

Psoriasis is a chronic, systemic, immune-mediated disease with an incidence of approximately 2%. The pathogenesis of the disease is complex and not yet fully understood. Genetic factors play a significant role in the pathogenesis of the disease. In predisposed individuals, multiple trigger factors may contribute to disease onset and exacerbations of symptoms. Environmental factors (stress, infections, certain medications, nicotinism, alcohol, obesity) play a significant role in the pathogenesis of psoriasis. In addition, epigenetic mechanisms are considered result in modulation of individual gene expression and an increased likelihood of the disease. Studies highlight the significant role of epigenetic factors in the etiology and pathogenesis of psoriasis. Epigenetic mechanisms in psoriasis include DNA methylation, histone modifications and non-coding RNAs. Epigenetic mechanisms induce gene expression changes under the influence of chemical modifications of DNA and histones, which alter chromatin structure and activate transcription factors of selected genes, thus leading to translation of new mRNA without affecting the DNA sequence. Epigenetic factors can regulate gene expression at the transcriptional (via histone modification, DNA methylation) and posttranscriptional levels (via microRNAs and long non-coding RNAs). This study aims to present and discuss the different epigenetic mechanisms in psoriasis based on a review of the available literature.

Epigenetic Dysregulation in Lymphoid Malignancies

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. SCI-29-SCI-29
Author(s):  
Kapil N. Bhalla
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Transcription Factors ◽  
Transformed Cells ◽  
Epigenetic Mechanisms ◽  
Methyl Transferase ◽  
Lymphoid Malignancies ◽  
Proliferation And Differentiation ◽  
Histone Methyl Transferase

Abstract Abstract SCI-29 Greater understanding of the role of the epigenetic mechanisms and cancer cell epigenome in the pathogenesis of cancer in general and lymphoid malignancies in particular has emerged, which is yielding insights into how to therapeutically target these novel mechanisms. Epigenetic mechanisms include histone modifications, DNA methylation, nucleosome remodeling and small non-coding RNAs. In transformed cells, the methylome involves global DNA hypomethylation mostly targeting DNA repeats, and hypermethylation of CpG islands in the promoter regions of TSGs. For example, methylation and silencing of cell cycle dependent kinase inhibitors p16 and p15, and of DNA repair protein MGMT, is observed in lymphoma. A disequilibrium in the lysine (K) acetylation/deacetylation of the N-terminal tail of the core histone (H) proteins due to increased histone deacetylase (HDAC) activity leads to aberrant transcription repression of genes involved in regulation of proliferation and differentiation of lymphoid progenitors in lymphoid malignancies. Additionally, increased HDAC levels and activity may directly deacetylate and modify the transcriptional activity of transcription factors, or HDACs may be recruited along with co-repressors by transcriptional repressors such as Bcl-6 to the promoters of the repressed genes in lymphoma. Histone lysine methylation, regulated by the reciprocal activity of a specific histone methyl transferase (HMTs) and histone de-methylase, also modifies gene expression based on the lysine residue that is affected. For example, increased levels and activity of the polycomb repressive complex (PRC) 2 protein EZH (enhancer of zeste) 2, a histone methyl transferase induces the repressive chromatin mark H3K27 trimethylation (me3), which is erased by the demethylase, UTX. Mutations in EZH2 and UTX have been observed in transformed cells. Conversely, the methylation status of the permissive chromatin mark H3K4me3 and gene expression is reciprocally controlled by the HMTase, MLL, and the demethylases JARID1A and LSD1. PRC1 protein, BMI-1, is over-expressed and implicated in lymphoid malignancies. Genetic abnormalities of cell fate transcription factors (CFTFs), e.g., MYB, PAX5 and IKAROS, which recruit PRC1 and PRC2 complexes and their member proteins, e.g., BMI and EZH2, also deregulate the expression of developmentally regulated genes involved in stem cell behavior, related to self-renewal, proliferation and differentiation of transformed cells. PRC proteins EZH2 and BMI, in turn, can recruit DNMTs and promote de novo DNA methylation of TSGs. Levels and activity of the non-coding small (MiRs 101 and 26a for EZH2; MiR 29 for DNMT3a and DNMT3b; and MiR15a and 16 for BMI) may also be deregulated in transformed cells. Interestingly, the levels of MiRs are epigenetically regulated. Collectively, the complex interplay of the epigenetic mechanisms in the pathogenesis of lymphoid malignancies underscores the importance of targeting the deregulated mechanisms in a combinatorial fashion. Inhibitors of chromatin modifying enzymes including HDACs and DNMTs are approved for therapy by the FDA and, given alone or in combination, have shown efficacy in clinical trials in hematologic malignancies. Combined inhibition of EZH2 and HDACs also displays anti-lymphoma and anti-leukemia synergy. In the presentation, the emerging knowledge related to the role of epigenetic mechanisms in the pathogenesis of lymphoid malignancies, as well as the potential for combined therapeutic targeting of the deregulated mechanisms will be highlighted. Disclosures: Bhalla: Novartis: Honoraria, Research Funding; Merck: Honoraria.

The role of DNA methylation: a challenge for the DOHaD paradigm in going beyond the historical debate

2014 ◽  
Vol 6 (1) ◽  
pp. 2-4 ◽  
Author(s):  
S. Ngo ◽  
A. Sheppard
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Gene Structure ◽  
Gene Activity ◽  
Epigenetic Mark ◽  
Epigenetic Mechanisms ◽  
Omics Technologies ◽  
Considerable Research ◽  
Parental Imprinting

A heritage of considerable research into such phenomena as parental imprinting and carcinogenesis is an almost axiomatic association of the DNA methylation epigenetic mark with the silencing of gene expression. However, the increasing technical resolution afforded by burgeoning -omics technologies reveals that a more elaborate interaction may exist between DNA methylation, within sub-regions of gene structure and/or specific dinucleotide sites, and levels of gene activity. Furthermore, seminal observations from the field of DOHaD, which clearly define the alignment of sequential epigenetic modifications and gene activity appear not to support a strictly causal relationship between DNA methylation and gene silencing. The temporal element implicit within DOHaD studies provides a useful framework within which to further explore the role of epigenetic mechanisms and in particular perhaps, to address the question of ‘deterministic intent’ when implicating the epigenetic regulation of gene activity in the manifestation of phenotype.

scholarly journals Cellular Heterogeneity–Adjusted cLonal Methylation (CHALM) improves prediction of gene expression

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jianfeng Xu ◽  
Jiejun Shi ◽  
Xiaodong Cui ◽  
Ya Cui ◽  
Jingyi Jessica Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Cellular Heterogeneity ◽  
Biological Functions ◽  
Global Correlation ◽  
Differentially Methylated Genes ◽  
Promoter Dna Methylation ◽  
Functional Consequences ◽  
Promoter Dna ◽  
Underlying Mechanisms

AbstractPromoter DNA methylation is a well-established mechanism of transcription repression, though its global correlation with gene expression is weak. This weak correlation can be attributed to the failure of current methylation quantification methods to consider the heterogeneity among sequenced bulk cells. Here, we introduce Cell Heterogeneity–Adjusted cLonal Methylation (CHALM) as a methylation quantification method. CHALM improves understanding of the functional consequences of DNA methylation, including its correlations with gene expression and H3K4me3. When applied to different methylation datasets, the CHALM method enables detection of differentially methylated genes that exhibit distinct biological functions supporting underlying mechanisms.

scholarly journals Stress Modifies the Expression of Glucocorticoid-Responsive Genes by Acting at Epigenetic Levels in the Rat Prefrontal Cortex: Modulatory Activity of Lurasidone

2021 ◽  
Vol 22 (12) ◽  
pp. 6197
Author(s):  
Paola Brivio ◽  
Giulia Sbrini ◽  
Letizia Tarantini ◽  
Chiara Parravicini ◽  
Piotr Gruca ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Chronic Stress ◽  
Chronic Mild Stress ◽  
Male Rats ◽  
Mild Stress ◽  
Experimental Conditions ◽  
Glucocorticoid Responsive Element ◽  
Responsive Element

Epigenetics is one of the mechanisms by which environmental factors can alter brain function and may contribute to central nervous system disorders. Alterations of DNA methylation and miRNA expression can induce long-lasting changes in neurobiological processes. Hence, we investigated the effect of chronic stress, by employing the chronic mild stress (CMS) and the chronic restraint stress protocol, in adult male rats, on the glucocorticoid receptor (GR) function. We focused on DNA methylation specifically in the proximity of the glucocorticoid responsive element (GRE) of the GR responsive genes Gadd45β, Sgk1, and Gilz and on selected miRNA targeting these genes. Moreover, we assessed the role of the antipsychotic lurasidone in modulating these alterations. Chronic stress downregulated Gadd45β and Gilz gene expression and lurasidone normalized the Gadd45β modification. At the epigenetic level, CMS induced hypermethylation of the GRE of Gadd45β gene, an effect prevented by lurasidone treatment. These stress-induced alterations were still present even after a period of rest from stress, indicating the enduring nature of such changes. However, the contribution of miRNA to the alterations in gene expression was moderate in our experimental conditions. Our results demonstrated that chronic stress mainly affects Gadd45β expression and methylation, effects that are prolonged over time, suggesting that stress leads to changes in DNA methylation that last also after the cessation of stress procedure, and that lurasidone is a modifier of such mechanisms.

Research progress in predicting DNA methylation modifications and the relation with human diseases

2021 ◽  
Vol 28 ◽  
Author(s):  
Chunyan Ao ◽  
Lin Gao ◽  
Liang Yu
Keyword(s):  
Dna Methylation ◽  
Eukaryotic Cell ◽  
Machine Learning Algorithms ◽  
Research Progress ◽  
Epigenetic Mechanisms ◽  
Biological Processes ◽  
Prediction Tools ◽  
Transformation Mechanisms ◽  
The Relationship ◽  
Treatment And Diagnosis

: DNA methylation is an important mode of regulation in epigenetic mechanisms, and it is one of the research foci in the field of epigenetics. DNA methylation modification affects a series of biological processes, such as eukaryotic cell growth, differentiation and transformation mechanisms, by regulating gene expression. In this review, we systematically summarized the DNA methylation databases, prediction tools for DNA methylation modification, machine learning algorithms for predicting DNA methylation modification, and the relationship between DNA methylation modification and diseases such as hypertension, Alzheimer's disease, diabetic nephropathy, and cancer. An in-depth understanding of DNA methylation mechanisms can promote accurate prediction of DNA methylation modifications and the treatment and diagnosis of related diseases.

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

Epigenomics ◽  
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.

Retrovirus-induced interference with collagen I gene expression in Mov13 fibroblasts is maintained in the absence of DNA methylation

1991 ◽  
Vol 11 (1) ◽  
pp. 47-54
Author(s):  
H Chan ◽  
S Hartung ◽  
M Breindl
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Chromatin Structure ◽  
Transcriptional Activity ◽  
Xenopus Laevis Oocytes ◽  
Regulatory Sequences ◽  
Type I ◽  
Wild Type ◽  
Col1a1 Gene

We have studied the role of DNA methylation in repression of the murine alpha 1 type I collagen (COL1A1) gene in Mov13 fibroblasts. In Mov13 mice, a retroviral provirus has inserted into the first intron of the COL1A1 gene and blocks its expression at the level of transcriptional initiation. We found that regulatory sequences in the COL1A1 promoter region that are involved in the tissue-specific regulation of the gene are unmethylated in collagen-expressing wild-type fibroblasts and methylated in Mov13 fibroblasts, confirming and extending earlier observations. To directly assess the role of DNA methylation in the repression of COL1A1 gene transcription, we treated Mov13 fibroblasts with the demethylating agent 5-azacytidine. This treatment resulted in a demethylation of the COL1A1 regulatory sequences but failed to activate transcription of the COL1A1 gene. Moreover, the 5-azacytidine treatment induced a transcription-competent chromatin structure in the retroviral sequences but not in the COL1A1 promoter. In DNA transfection and microinjection experiments, we found that the provirus interfered with transcriptional activity of the COL1A1 promoter in Mov13 fibroblasts but not in Xenopus laevis oocytes. In contrast, the wild-type COL1A1 promoter was transcriptionally active in Mov13 fibroblasts. These experiments showed that the COL1A1 promoter is potentially transcriptionally active in the presence of proviral sequences and that Mov13 fibroblasts contain the trans-acting factors required for efficient COL1A1 gene expression. Our results indicate that the provirus insertion in Mov13 can inactivate COL1A1 gene expression at several levels. It prevents the developmentally regulated establishment of a transcription-competent methylation pattern and chromatin structure of the COL1A1 domain and, in the absence of DNA methylation, appears to suppress the COL1A1 promoter in a cell-specific manner, presumably by assuming a dominant chromatin structure that may be incompatible with transcriptional activity of flanking cellular sequences.

scholarly journals Epigenetic mechanisms in sexual differentiation of the brain and behaviour

2016 ◽  
Vol 371 (1688) ◽  
pp. 20150114 ◽  
Author(s):  
Nancy G. Forger
Keyword(s):  
Gene Expression ◽  
Sex Differences ◽  
Sexual Differentiation ◽  
Wide Distribution ◽  
Epigenetic Modifications ◽  
Epigenetic Mechanism ◽  
Epigenetic Mechanisms ◽  
Genome Wide ◽  
The Brain

Circumstantial evidence alone argues that the establishment and maintenance of sex differences in the brain depend on epigenetic modifications of chromatin structure. More direct evidence has recently been obtained from two types of studies: those manipulating a particular epigenetic mechanism, and those examining the genome-wide distribution of specific epigenetic marks. The manipulation of histone acetylation or DNA methylation disrupts the development of several neural sex differences in rodents. Taken together, however, the evidence suggests there is unlikely to be a simple formula for masculine or feminine development of the brain and behaviour; instead, underlying epigenetic mechanisms may vary by brain region or even by dependent variable within a region. Whole-genome studies related to sex differences in the brain have only very recently been reported, but suggest that males and females may use different combinations of epigenetic modifications to control gene expression, even in cases where gene expression does not differ between the sexes. Finally, recent findings are discussed that are likely to direct future studies on the role of epigenetic mechanisms in sexual differentiation of the brain and behaviour.

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