The Role of Sulforaphane in Epigenetic Mechanisms, Including Interdependence between Histone Modification and DNA Methylation

Abstract Epigenetics encapsulates a group of molecular mechanisms including DNA methylation, histone modification and microRNAs (miRNAs). Gestational diabetes (GDM) increases the risk of adverse perinatal outcomes and is associated with future offspring risk of obesity and type 2 diabetes. It has been hypothesised that epigenetic mechanisms mediate an effect of GDM on offspring adiposity and type 2 diabetes and this could provide a modifiable mechanism to reduce type 2 diabetes in the next generation. Evidence for this hypothesis is lacking. Epigenetic epidemiology could also contribute to reducing type 2 diabetes by identifying biomarkers that accurately predict risk of GDM and its associated future adverse outcomes. We reviewed published human studies that explored associations between any of maternal GDM, type 2 diabetes, gestational fasting or post-load glucose and any epigenetic marker (DNA methylation, histone modification or miRNA). Of the 81 relevant studies we identified, most focused on the potential role of epigenetic mechanisms in mediating intrauterine effects of GDM on offspring outcomes. Studies were small (median total number of participants 58; median number of GDM cases 27) and most did not attempt replication. The most common epigenetic measure analysed was DNA methylation. Most studies that aimed to explore epigenetic mediation examined associations of in utero exposure to GDM with offspring cord or infant blood/placenta DNA methylation. Exploration of any causal effect, or effect on downstream offspring outcomes, was lacking. There is a need for more robust methods to explore the role of epigenetic mechanisms as possible mediators of effects of exposure to GDM on future risk of obesity and type 2 diabetes. Research to identify epigenetic biomarkers to improve identification of women at risk of GDM and its associated adverse (maternal and offspring) outcomes is currently rare but could contribute to future tools for accurate risk stratification.

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DNA methylation regulates transcriptional homeostasis of algal endosymbiosis in the coral modelAiptasia

10.1101/213066 ◽

2017 ◽

Cited By ~ 3

Author(s):

Yong Li ◽

Yi Jin Liew ◽

Guoxin Cui ◽

Maha J Cziesielski ◽

Noura Zahran ◽

...

Keyword(s):

Dna Methylation ◽

Molecular Mechanisms ◽

Model System ◽

Epigenetic Mechanism ◽

Symbiotic Relationship ◽

Epigenetic Mechanisms ◽

Genome Wide ◽

Spurious Transcription ◽

Coral Reef Ecosystems

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.

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Intergenerational epigenetic inheritance in reef-building corals

10.1101/269076 ◽

2018 ◽

Cited By ~ 6

Author(s):

Yi Jin Liew ◽

Emily J. Howells ◽

Xin Wang ◽

Craig T. Michell ◽

John A. Burt ◽

...

Keyword(s):

Dna Methylation ◽

Intergenerational Transmission ◽

Epigenetic Inheritance ◽

Cpg Methylation ◽

Epigenetic Mechanisms ◽

Transgenerational Inheritance ◽

Genome Wide ◽

Methylation Patterns ◽

Hypermethylated Genes

MainThe notion that intergenerational or transgenerational inheritance operates solely through genetic means is slowly being eroded: epigenetic mechanisms have been shown to induce heritable changes in gene activity in plants1,2and metazoans1,3. Inheritance of DNA methylation provides a potential pathway for environmentally induced phenotypes to contribute to evolution of species and populations1–4. However, in basal metazoans, it is unknown whether inheritance of CpG methylation patterns occurs across the genome (as in plants) or as rare exceptions (as in mammals)4. Here, we demonstrate genome-wide intergenerational transmission of CpG methylation patterns from parents to sperm and larvae in a reef-building coral. We also show variation in hypermethylated genes in corals from distinct environments, indicative of responses to variations in temperature and salinity. These findings support a role of DNA methylation in the transgenerational inheritance of traits in corals, which may extend to enhancing their capacity to adapt to climate change.

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The role of microRNA in myelodysplastic syndromes: beyond DNA methylation and histone modification

European Journal Of Haematology ◽

10.1111/ejh.12735 ◽

2016 ◽

Vol 96 (6) ◽

pp. 553-563 ◽

Cited By ~ 4

Author(s):

Vibor Milunović ◽

Inga Mandac Rogulj ◽

Ana Planinc-Peraica ◽

Ekaterina Bulycheva ◽

Slobodanka Kolonić Ostojić

Keyword(s):

Dna Methylation ◽

Histone Modification ◽

Myelodysplastic Syndromes

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The Roles of Epigenetics Regulation in Bone Metabolism and Osteoporosis

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.619301 ◽

2021 ◽

Vol 8 ◽

Author(s):

Fei Xu ◽

Wenhui Li ◽

Xiao Yang ◽

Lixin Na ◽

Linjun Chen ◽

...

Keyword(s):

Dna Methylation ◽

Histone Modification ◽

Osteogenic Differentiation ◽

Bone Metabolism ◽

Bone Fragility ◽

Research Progress ◽

Epigenetic Mechanisms ◽

Mineral Density ◽

Transcriptional Regulatory ◽

Non Coding Rnas

Osteoporosis is a metabolic disease characterized by decreased bone mineral density and the destruction of bone microstructure, which can lead to increased bone fragility and risk of fracture. In recent years, with the deepening of the research on the pathological mechanism of osteoporosis, the research on epigenetics has made significant progress. Epigenetics refers to changes in gene expression levels that are not caused by changes in gene sequences, mainly including DNA methylation, histone modification, and non-coding RNAs (lncRNA, microRNA, and circRNA). Epigenetics play mainly a post-transcriptional regulatory role and have important functions in the biological signal regulatory network. Studies have shown that epigenetic mechanisms are closely related to osteogenic differentiation, osteogenesis, bone remodeling and other bone metabolism-related processes. Abnormal epigenetic regulation can lead to a series of bone metabolism-related diseases, such as osteoporosis. Considering the important role of epigenetic mechanisms in the regulation of bone metabolism, we mainly review the research progress on epigenetic mechanisms (DNA methylation, histone modification, and non-coding RNAs) in the osteogenic differentiation and the pathogenesis of osteoporosis to provide a new direction for the treatment of bone metabolism-related diseases.

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Unfolding the pathogenesis of systemic sclerosis through epigenomics

STEMedicine ◽

10.37175/stemedicine.v1i1.5 ◽

2020 ◽

Vol 1 (1) ◽

pp. e5

Author(s):

Xiuzhi Jia ◽

Hao Cheng ◽

Ying Xiao

Keyword(s):

Dna Methylation ◽

Systemic Sclerosis ◽

Autoimmune Diseases ◽

Environmental Stress ◽

Histone Modification ◽

Immune Dysregulation ◽

Epigenetic Mechanisms ◽

Internal Organs ◽

Current Information ◽

Epigenetic Alteration

As a group of autoimmune diseases, systemic sclerosis (scleroderma, SSc) is characterized by immune dysregulation, micro-vessels dominant obliteration, and the final fibrosis of the skin and or internal organs. Although the precise mechanisms are still unknown, increasing data shows that epigenetic mechanisms, such as DNA methylation, histone modification, and microRNA (miRNA), are strictly related to the pathogenesis of scleroderma. Epigenetic mechanisms, which can link genetics and environmental stress, represents a promising field in systemic sclerosis investigation. The objective of this review is, to sum up the current information about epigenetic alteration.

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The role of histone modifications and DNA methylation in renal cell carcinoma development

Ecological genetics ◽

10.17816/ecogen10359-76 ◽

2012 ◽

Vol 10 (3) ◽

pp. 59-76

Author(s):

Lilia R Kutlyeva ◽

Irina R Gilayzova ◽

Rita I Khusainova ◽

Elsa K Khusnutdinova

Keyword(s):

Dna Methylation ◽

Renal Cell Carcinoma ◽

Gene Regulation ◽

Cell Carcinoma ◽

Genomic Imprinting ◽

Histone Modifications ◽

Renal Cell ◽

Human Cancer ◽

Epigenetic Mechanisms

Epigenetic mechanisms of gene regulation play a key role in carcinogenesis. This review will focus on the recent advances of epigenetic investigations in the development of human cancer. The role of histone modifications, genomic imprinting and DNA methylation in renal cell carcinoma development and progression will be considered.

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The role of epigenetics, particularly DNA methylation, in the evolution of caste in insect societies

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2020.0115 ◽

2021 ◽

Vol 376 (1826) ◽

Cited By ~ 2

Author(s):

Benjamin P. Oldroyd ◽

Boris Yagound

Keyword(s):

Dna Methylation ◽

Developmental Trajectories ◽

Epigenetic Mechanisms ◽

Theme Issue ◽

Eusocial Insects ◽

Insect Societies ◽

Divergent Development ◽

Worker Castes ◽

Epigenetic Processes

Eusocial insects can be defined as those that live in colonies and have distinct queens and workers. For most species, queens and workers arise from a common genome, and so caste-specific developmental trajectories must arise from epigenetic processes. In this review, we examine the epigenetic mechanisms that may be involved in the regulation of caste dimorphism. Early work on honeybees suggested that DNA methylation plays a causal role in the divergent development of queen and worker castes. This view has now been challenged by studies that did not find consistent associations between methylation and caste in honeybees and other species. Evidence for the involvement of methylation in modulating behaviour of adult workers is also inconsistent. Thus, the functional significance of DNA methylation in social insects remains equivocal. This article is part of the theme issue ‘How does epigenetics influence the course of evolution?’

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The Role of DNA Methylation and Histone Modification in Periodontal Disease: A Systematic Review

International Journal of Molecular Sciences ◽

10.3390/ijms21176217 ◽

2020 ◽

Vol 21 (17) ◽

pp. 6217

Author(s):

Ismael Khouly ◽

Rosalie Salus Braun ◽

Michelle Ordway ◽

Bradley Eric Aouizerat ◽

Iya Ghassib ◽

...

Keyword(s):

Systematic Review ◽

Dna Methylation ◽

Periodontal Disease ◽

Histone Modification ◽

Histone Modifications ◽

Disease Risk ◽

Periodontal Diseases ◽

Epigenetic Changes ◽

Human Adults

Despite a number of reports in the literature on the role of epigenetic mechanisms in periodontal disease, a thorough assessment of the published studies is warranted to better comprehend the evidence on the relationship between epigenetic changes and periodontal disease and its treatment. Therefore, the aim of this systematic review is to identify and synthesize the evidence for an association between DNA methylation/histone modification and periodontal disease and its treatment in human adults. A systematic search was independently conducted to identify articles meeting the inclusion criteria. DNA methylation and histone modifications associated with periodontal diseases, gene expression, epigenetic changes after periodontal therapy, and the association between epigenetics and clinical parameters were evaluated. Sixteen studies were identified. All included studies examined DNA modifications in relation to periodontitis, and none of the studies examined histone modifications. Substantial variation regarding the reporting of sample sizes and patient characteristics, statistical analyses, and methodology, was found. There was some evidence, albeit inconsistent, for an association between DNA methylation and periodontal disease. IL6, IL6R, IFNG, PTGS2, SOCS1, and TNF were identified as candidate genes that have been assessed for DNA methylation in periodontitis. While several included studies found associations between methylation levels and periodontal disease risk, there is insufficient evidence to support or refute an association between DNA methylation and periodontal disease/therapy in human adults. Further research must be conducted to identify reproducible epigenetic markers and determine the extent to which DNA methylation can be applied as a clinical biomarker.

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The Epigenetic Landscape of Vascular Calcification: An Integrative Perspective

International Journal of Molecular Sciences ◽

10.3390/ijms21030980 ◽

2020 ◽

Vol 21 (3) ◽

pp. 980 ◽

Cited By ~ 9

Author(s):

Yi-Chou Hou ◽

Chien-Lin Lu ◽

Tzu-Hang Yuan ◽

Min-Tser Liao ◽

Chia-Ter Chao ◽

...

Keyword(s):

Dna Methylation ◽

Histone Modification ◽

Vascular Calcification ◽

Calcium Deposition ◽

Non Coding Rna ◽

Physico Chemical ◽

Variable Combination ◽

Epigenetic Signatures ◽

Epigenetic Processes

Vascular calcification (VC) is an important complication among patients of advanced age, those with chronic kidney disease, and those with diabetes mellitus. The pathophysiology of VC encompasses passive occurrence of physico-chemical calcium deposition, active cellular secretion of osteoid matrix upon exposure to metabolically noxious stimuli, or a variable combination of both processes. Epigenetic alterations have been shown to participate in this complex environment, through mechanisms including DNA methylation, non-coding RNAs, histone modifications, and chromatin changes. Despite such importance, existing reviews fail to provide a comprehensive view of all relevant reports addressing epigenetic processes in VC, and cross-talk between different epigenetic machineries is rarely examined. We conducted a systematic review based on PUBMED and MEDLINE databases up to 30 September 2019, to identify clinical, translational, and experimental reports addressing epigenetic processes in VC; we retrieved 66 original studies, among which 60.6% looked into the pathogenic role of non-coding RNA, followed by DNA methylation (12.1%), histone modification (9.1%), and chromatin changes (4.5%). Nine (13.6%) reports examined the discrepancy of epigenetic signatures between subjects or tissues with and without VC, supporting their applicability as biomarkers. Assisted by bioinformatic analyses blending in each epigenetic component, we discovered prominent interactions between microRNAs, DNA methylation, and histone modification regarding potential influences on VC risk.

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