-
Cells Aug 2019Rheumatoid arthritis (RA) is a long-term autoimmune disease of unknown etiology that leads to progressive joint destruction and ultimately to disability. RA affects as... (Review)
Review
Rheumatoid arthritis (RA) is a long-term autoimmune disease of unknown etiology that leads to progressive joint destruction and ultimately to disability. RA affects as much as 1% of the population worldwide. To date, RA is not a curable disease, and the mechanisms responsible for RA development have not yet been well understood. The development of more effective treatments and improvements in the early diagnosis of RA is direly needed to increase patients' functional capacity and their quality of life. As opposed to genetic mutation, epigenetic changes, such as DNA methylation, are reversible, making them good therapeutic candidates, modulating the immune response or aggressive synovial fibroblasts (FLS-fibroblast-like synoviocytes) activity when it is necessary. It has been suggested that DNA methylation might contribute to RA development, however, with insufficient and conflicting results. Besides, recent studies have shown that circulating cell-free methylated DNA (ccfDNA) in blood offers a very convenient, non-invasive, and repeatable "liquid biopsy", thus providing a reliable template for assessing molecular markers of various diseases, including RA. Thus, epigenetic therapies controlling autoimmunity and systemic inflammation may find wider implications for the diagnosis and management of RA. In this review, we highlight current challenges associated with the treatment of RA and other autoimmune diseases and discuss how targeting DNA methylation may improve diagnostic, prognostic, and therapeutic approaches.
Topics: Animals; Arthritis, Rheumatoid; DNA Methylation; Humans
PubMed: 31443448
DOI: 10.3390/cells8090953 -
Clinical Epigenetics Apr 2021Congenital heart disease (CHD) is a common structural birth defect worldwide, and defects typically occur in the walls and valves of the heart or enlarged blood vessels.... (Review)
Review
Congenital heart disease (CHD) is a common structural birth defect worldwide, and defects typically occur in the walls and valves of the heart or enlarged blood vessels. Chromosomal abnormalities and genetic mutations only account for a small portion of the pathogenic mechanisms of CHD, and the etiology of most cases remains unknown. The role of epigenetics in various diseases, including CHD, has attracted increased attention. The contributions of DNA methylation, one of the most important epigenetic modifications, to CHD have not been illuminated. Increasing evidence suggests that aberrant DNA methylation is related to CHD. Here, we briefly introduce DNA methylation and CHD and then review the DNA methylation profiles during cardiac development and in CHD, abnormalities in maternal genome-wide DNA methylation patterns are also described. Whole genome methylation profile and important differentially methylated genes identified in recent years are summarized and clustered according to the sample type and methodologies. Finally, we discuss the novel technology for and prospects of CHD-related DNA methylation.
Topics: DNA Methylation; Epigenesis, Genetic; Heart Defects, Congenital; Humans
PubMed: 33902696
DOI: 10.1186/s13148-021-01077-7 -
Development (Cambridge, England) Dec 2022DNA methylation is a highly conserved epigenetic modification that plays essential roles in mammalian gene regulation, genome stability and development. Despite being... (Review)
Review
DNA methylation is a highly conserved epigenetic modification that plays essential roles in mammalian gene regulation, genome stability and development. Despite being primarily considered a stable and heritable epigenetic silencing mechanism at heterochromatic and repetitive regions, whole genome methylome analysis reveals that DNA methylation can be highly cell-type specific and dynamic within proximal and distal gene regulatory elements during early embryonic development, stem cell differentiation and reprogramming, and tissue maturation. In this Review, we focus on the mechanisms and functions of regulated DNA methylation and demethylation, highlighting how these dynamics, together with crosstalk between DNA methylation and histone modifications at distinct regulatory regions, contribute to mammalian development and tissue maturation. We also discuss how recent technological advances in single-cell and long-read methylome sequencing, along with targeted epigenome-editing, are enabling unprecedented high-resolution and mechanistic dissection of DNA methylome dynamics.
Topics: Animals; Epigenome; DNA Methylation; Epigenesis, Genetic; Histone Code; Mammals
PubMed: 36519514
DOI: 10.1242/dev.182683 -
Archives of Pharmacal Research Feb 2019Cancer can be identified as a chaotic cell state, which breaks the rules that govern growth and reproduction, with main characteristics such as uncontrolled division,... (Review)
Review
Cancer can be identified as a chaotic cell state, which breaks the rules that govern growth and reproduction, with main characteristics such as uncontrolled division, invading other tissues, usurping resources, and eventually killing its host. It was once believed that cancer is caused by a progressive series of genetic aberrations, and certain mutations of genes, including oncogenes and tumor suppressor genes, have been identified as the cause of cancer. However, piling evidence suggests that epigenetic modifications working in concert with genetic mechanisms to regulate transcriptional activity are dysregulated in many diseases, including cancer. Cancer epigenetics explain a wide range of heritable changes in gene expression, which do not come from any alteration in DNA sequences. Aberrant DNA methylation, histone modifications, and expression of long non-coding RNAs (lncRNAs) are key epigenetic mechanisms associated with tumor initiation, cancer progression, and metastasis. Within the past decade, cancer epigenetics have enabled us to develop novel biomarkers and therapeutic target for many types of cancers. In this review, we will summarize the major epigenetic changes involved in cancer biology along with clinical and preclinical results developed as novel cancer therapeutics.
Topics: Animals; DNA Methylation; Epigenesis, Genetic; Genetic Therapy; Histones; Humans; Neoplasms
PubMed: 30806885
DOI: 10.1007/s12272-019-01126-z -
Discovery Medicine 2021Cardiovascular disease (CVD) is a top public health problem especially for the elderly. Atherosclerosis is the pathological basis of CVD. Many studies have shown that...
Cardiovascular disease (CVD) is a top public health problem especially for the elderly. Atherosclerosis is the pathological basis of CVD. Many studies have shown that epigenetics plays a key role in regulating the development of atherosclerotic disease. Epigenetics includes DNA methylation, histone modification, RNA methylation, and non-coding RNA. More and more epigenetic regulations are confirmed to take part in heart development, response to stress, and endothelial injury, it is even suggested that atherosclerosis is the result of abnormal epigenetic regulation. Researchers have performed studies on novel drugs through epigenetic modification, yielding varied results. It is necessary to explore a range of epigenetic mechanisms to explain the causes and progression of atherosclerosis and uncover new targets for treatment. This article summarizes the latest development of epigenetic modification and its effect on the occurrence and progression of atherosclerosis and the possible prevention and treatment modalities of atherosclerosis that these research findings would engender.
Topics: Aged; Atherosclerosis; Cardiovascular Diseases; DNA Methylation; Epigenesis, Genetic; Humans
PubMed: 34965371
DOI: No ID Found -
Swiss Medical Weekly 2013DNA methylation, the addition of a methyl group to cytosines and adenosines, regulates gene expression on a level that is usually referred to as epigenetic, that is,... (Review)
Review
DNA methylation, the addition of a methyl group to cytosines and adenosines, regulates gene expression on a level that is usually referred to as epigenetic, that is, stably maintained during cell divisions. In humans, aberrant DNA methylation is associated with several malignancies, including cancer and so-called imprinting disorders, making it an attractive target for diagnostic purposes. Here we give a brief introduction to the biology of DNA methylation and present the use of methylation biomarkers in laboratory medicine. DNA methylation assays have become the standard procedure in the diagnosis of imprinting disorders, and they are about to shift cancer diagnostics and prognostics to the next level of molecular medicine. However, there is evidence of problems associated with the introduction of such cancer assays in routine diagnostics. We review several assays that have been proposed for DNA methylation analysis. The assays presented analyse the methylation status of single loci and are based either on a bisulphite-treatment or on methylation-sensitive restriction of the DNA under investigation.
Topics: DNA; DNA Methylation; Epigenesis, Genetic; Genomic Imprinting; Humans; Neoplasms; Polymerase Chain Reaction; Sulfites
PubMed: 23740463
DOI: 10.4414/smw.2013.13799 -
Journal of Translational Medicine Mar 2023Fibrosis, a process caused by excessive deposition of extracellular matrix (ECM), is a common cause and outcome of organ failure and even death. Researchers have made... (Review)
Review
Fibrosis, a process caused by excessive deposition of extracellular matrix (ECM), is a common cause and outcome of organ failure and even death. Researchers have made many efforts to understand the mechanism of fibrogenesis and to develop therapeutic strategies; yet, the outcome remains unsatisfactory. In recent years, advances in epigenetics, including chromatin remodeling, histone modification, DNA methylation, and noncoding RNA (ncRNA), have provided more insights into the fibrotic process and have suggested the possibility of novel therapy for organ fibrosis. In this review, we summarize the current research on the epigenetic mechanisms involved in organ fibrosis and their possible clinical applications.
Topics: Humans; Epigenesis, Genetic; DNA Methylation; Extracellular Matrix; Protein Processing, Post-Translational; Research Personnel
PubMed: 36864460
DOI: 10.1186/s12967-023-04018-5 -
Clinical Epigenetics Dec 2021The role of breastfeeding in modulating epigenetic factors has been suggested as a possible mechanism conferring its benefits on child development but it lacks evidence....
BACKGROUND
The role of breastfeeding in modulating epigenetic factors has been suggested as a possible mechanism conferring its benefits on child development but it lacks evidence. Using extensive DNA methylation data from the ALSPAC child cohort, we characterized the genome-wide landscape of DNA methylation variations associated with the duration of exclusive breastfeeding and assessed whether these variations mediate the association between exclusive breastfeeding and BMI over different epochs of child growth.
RESULTS
Exclusive breastfeeding elicits more substantial DNA methylation variations during infancy than at other periods of child growth. At the genome-wide level, 13 CpG sites in girls (miR-21, SNAPC3, ATP6V0A1, DHX15/PPARGC1A, LINC00398/ALOX5AP, FAM238C, NATP/NAT2, CUX1, TRAPPC9, OSBPL1A, ZNF185, FAM84A, PDPK1) and 2 CpG sites in boys (IL16 and NREP), mediate the association between exclusive breastfeeding and longitudinal BMI. We found enrichment of CpG sites located within miRNAs and key pathways (AMPK signaling pathway, insulin signaling pathway, endocytosis). Overall DNA methylation variation corresponding to 3 to 5 months of exclusive breastfeeding was associated with slower BMI growth the first 6 years of life compared to no breastfeeding and in a dose-response manner with exclusive breastfeeding duration.
CONCLUSIONS
Our study confirmed the early postnatal period as a critical developmental period associated with substantial DNA methylation variations, which in turn could mitigate the development of overweight and obesity from infancy to early childhood. Since an accelerated growth during these developmental periods has been linked to the development of sustained obesity later in life, exclusive breastfeeding could have a major role in preventing the risks of overweight/obesity and children and adults through DNA methylation mechanisms occurring early in life.
Topics: Age Factors; Body Mass Index; Breast Feeding; Child; Child, Preschool; Correlation of Data; DNA Methylation; Female; Genome-Wide Association Study; Growth Disorders; Humans; Male
PubMed: 34937578
DOI: 10.1186/s13148-021-01209-z -
Bone Mar 2016Although there is a documented social gradient for osteoporosis, the underlying mechanism(s) for that gradient remain unknown. We propose a conceptual model based upon... (Review)
Review
INTRODUCTION
Although there is a documented social gradient for osteoporosis, the underlying mechanism(s) for that gradient remain unknown. We propose a conceptual model based upon the allostatic load theory, to suggest how DNA methylation (DNAm) might underpin the social gradient in osteoporosis and fracture. We hypothesise that social disadvantage is associated with priming of inflammatory pathways mediated by epigenetic modification that leads to an enhanced state of inflammatory reactivity and oxidative stress, and thus places socially disadvantaged individuals at greater risk of osteoporotic fracture.
METHODS/RESULTS
Based on a review of the literature, we present a conceptual model in which social disadvantage increases stress throughout the lifespan, and engenders a proinflammatory epigenetic signature, leading to a heightened inflammatory state that increases risk for osteoporotic fracture in disadvantaged groups that are chronically stressed.
CONCLUSIONS
Our model proposes that, in addition to the direct biological effects exerted on bone by factors such as physical activity and nutrition, the recognised socially patterned risk factors for osteoporosis also act via epigenetic-mediated dysregulation of inflammation. DNAm is a dynamic modulator of gene expression with considerable relevance to the field of osteoporosis. Elucidating the extent to which this epigenetic mechanism transduces the psycho-social environment to increase the risk of osteoporotic fracture may yield novel entry points for intervention that can be used to reduce individual and population-wide risks for osteoporotic fracture. Specifically, an epigenetic evidence-base may strengthen the importance of lifestyle modification and stress reduction programs, and help to reduce health inequities across social groups.
MINI ABSTRACT
Our conceptual model proposes how DNA methylation might underpin the social gradient in osteoporotic fracture. We suggest that social disadvantage is associated with priming of inflammatory signalling pathways, which is mediated by epigenetic modifications, leading to a chronically heightened inflammatory state that places disadvantaged individuals at greater risk of osteoporosis.
Topics: Aging; DNA Methylation; Epigenesis, Genetic; Humans; Models, Biological; Osteoporotic Fractures; Socioeconomic Factors
PubMed: 26723576
DOI: 10.1016/j.bone.2015.12.015 -
Heredity Jul 2010Epigenetics investigates heritable changes in gene expression that occur without changes in DNA sequence. Several epigenetic mechanisms, including DNA methylation and... (Review)
Review
Epigenetics investigates heritable changes in gene expression that occur without changes in DNA sequence. Several epigenetic mechanisms, including DNA methylation and histone modifications, can change genome function under exogenous influence. We review current evidence indicating that epigenetic alterations mediate effects caused by exposure to environmental toxicants. Results obtained from animal models indicate that in utero or early-life environmental exposures produce effects that can be inherited transgenerationally and are accompanied by epigenetic alterations. The search for human equivalents of the epigenetic mechanisms identified in animal models is under way. Recent investigations have identified a number of environmental toxicants that cause altered methylation of human repetitive elements or genes. Some exposures can alter epigenetic states and the same and/or similar epigenetic alterations can be found in patients with the disease of concern. On the basis of current evidence, we propose possible models for the interplay between environmental exposures and the human epigenome. Several investigations have examined the relationship between exposure to environmental chemicals and epigenetics, and have identified toxicants that modify epigenetic states. Whether environmental exposures have transgenerational epigenetic effects in humans remains to be elucidated. In spite of the current limitations, available evidence supports the concept that epigenetics holds substantial potential for furthering our understanding of the molecular mechanisms of environmental toxicants, as well as for predicting health-related risks due to conditions of environmental exposure and individual susceptibility.
Topics: Animals; DNA Methylation; Disease Models, Animal; Disease Susceptibility; Environmental Exposure; Environmental Pollutants; Epigenesis, Genetic; Humans
PubMed: 20179736
DOI: 10.1038/hdy.2010.2