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Molecular Ecology Nov 2021DNA methylation is an ancient epigenetic pathway found across eukaryotes. Nevertheless, the targets of DNA methylation within genomes evolve extremely rapidly....
DNA methylation is an ancient epigenetic pathway found across eukaryotes. Nevertheless, the targets of DNA methylation within genomes evolve extremely rapidly. Arthropods display many such examples. The mealybug Planococcus citri has evolved methylation at promoter sequences, associated with gene silencing just as in mammals. In this issue of Molecular Ecology, Bain et al. (2021), thoroughly characterise mealybug methylation, exploring its potential functions in gene expression and the spectacular sexual dimorphism that is a characteristic of this species. Their results provide new insights into the complex relationship between DNA methylation and gene expression and highlight how rapidly different methylation systems can evolve.
Topics: Animals; Arthropods; DNA Methylation; Genome; Promoter Regions, Genetic; Sex Characteristics
PubMed: 34687580
DOI: 10.1111/mec.16243 -
Current Medicinal Chemistry 2020DNA methylation is considered as a crucial part of epigenetic modifications and a popular research topic in recent decades. It usually occurs with a methyl group adding... (Review)
Review
DNA methylation is considered as a crucial part of epigenetic modifications and a popular research topic in recent decades. It usually occurs with a methyl group adding to the fifth carbon atom of cytosine while the base sequence of DNA remains unchanged. DNA methylation has significant influences on maintaining cell functions, genetic imprinting, embryonic development and tumorigenesis procedures and hence the analysis of DNA methylation is of great medical significance. With the development of analytical techniques and further research on DNA methylation, numerous DNA methylation detection strategies based on biosensing technology have been developed to fulfill various study requirements. This article reviewed the development of electrochemistry and optical biosensing analysis of DNA methylation in recent years; in addition, we also reviewed some recent advances in the detection of DNA methylation using new techniques, such as nanopore biosensors, and highlighted the key technical and biological challenges involved in these methods. We hope this paper will provide useful information for the selection and establishment of analysis of DNA methylation.
Topics: Biosensing Techniques; DNA; DNA Methylation; Epigenesis, Genetic
PubMed: 31480993
DOI: 10.2174/0929867326666190903161750 -
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 -
Briefings in Functional Genomics Sep 2021The methylation of cytosine residues that precede adenine/thymine or other cytosine nucleotides instead of guanine in DNA is known as non-CpG methylation. It is a... (Review)
Review
The methylation of cytosine residues that precede adenine/thymine or other cytosine nucleotides instead of guanine in DNA is known as non-CpG methylation. It is a pronounced epigenetic modification with a central role in gene regulation similar to CpG methylation. Due to technological limitations, the locus-specific role of non-CpG methylation was scarcely understood. At present, high-throughput analyses and improved enrichment methods can elucidate the role of genome-wide non-CpG methylation distributions. Although the functional basis of non-CpG methylation in regulating gene expression control is known, its role in cancer development is yet to be ascertained. This review sheds light on the possible mechanism of non-CpG methylation in embryos and developed tissues with a special focus on cancer development and progression. In particular, the maintenance and alteration of non-CpG methylation levels and the crucial factors that determine this level of non-CpG methylation and its functional role in cancer are discussed.
Topics: CpG Islands; DNA; DNA Methylation; Epigenesis, Genetic; Humans; Neoplasms
PubMed: 34318313
DOI: 10.1093/bfgp/elab035 -
Clinical Epigenetics May 2024DNA methylation influences gene expression and function in the pathophysiology of type 2 diabetes mellitus (T2DM). Mapping of T2DM-associated DNA methylation could aid...
OBJECTIVE
DNA methylation influences gene expression and function in the pathophysiology of type 2 diabetes mellitus (T2DM). Mapping of T2DM-associated DNA methylation could aid early detection and/or therapeutic treatment options for diabetics.
DESIGN
A systematic literature search for associations between T2DM and DNA methylation was performed. Prospero registration ID: CRD42020140436.
METHODS
PubMed and ScienceDirect databases were searched (till October 19, 2023). Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and New Castle Ottawa scale were used for reporting the selection and quality of the studies, respectively.
RESULT
Thirty-two articles were selected. Four of 130 differentially methylated genes in blood, adipose, liver or pancreatic islets (TXNIP, ABCG1, PPARGC1A, PTPRN2) were reported in > 1 study. TXNIP was hypomethylated in diabetic blood across ethnicities. Gene enrichment analysis of the differentially methylated genes highlighted relevant disease pathways (T2DM, type 1 diabetes and adipocytokine signaling). Three prospective studies reported association of methylation in IGFBP2, MSI2, FTO, TXNIP, SREBF1, PHOSPHO1, SOCS3 and ABCG1 in blood at baseline with incident T2DM/hyperglycemia. Sex-specific differential methylation was reported only for HOOK2 in visceral adipose tissue (female diabetics: hypermethylated, male diabetics: hypomethylated). Gene expression was inversely associated with methylation status in 8 studies, in genes including ABCG1 (blood), S100A4 (adipose tissue), PER2 (pancreatic islets), PDGFA (liver) and PPARGC1A (skeletal muscle).
CONCLUSION
This review summarizes available evidence for using DNA methylation patterns to unravel T2DM pathophysiology. Further validation studies in diverse populations will set the stage for utilizing this knowledge for identifying early diagnostic markers and novel druggable pathways.
Topics: Female; Humans; Male; Carrier Proteins; Diabetes Mellitus, Type 2; DNA Methylation; Epigenesis, Genetic
PubMed: 38755631
DOI: 10.1186/s13148-024-01670-6 -
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 -
Essays in Biochemistry Dec 2019Cytosine methylation is a DNA modification that is critical for vertebrate development and provides a plastic yet stable information module in addition to the DNA code.... (Review)
Review
Cytosine methylation is a DNA modification that is critical for vertebrate development and provides a plastic yet stable information module in addition to the DNA code. DNA methylation memory establishment, maintenance and erasure is carefully balanced by molecular machinery highly conserved among vertebrates. In mammals, extensive erasure of epigenetic marks, including 5-methylcytosine (5mC), is a hallmark of early embryo and germline development. Conversely, global cytosine methylation patterns are preserved in at least some non-mammalian vertebrates over comparable developmental windows. The evolutionary mechanisms which drove this divergence are unknown, nevertheless a direct consequence of retaining epigenetic memory in the form of 5mC is the enhanced potential for transgenerational epigenetic inheritance (TEI). Given that DNA methylation dynamics remains underexplored in most vertebrate lineages, the extent of information transferred to offspring by epigenetic modification might be underestimated.
Topics: Animals; DNA; DNA Methylation; Embryo, Mammalian; Embryo, Nonmammalian; Epigenesis, Genetic; Gametogenesis; Genome; Humans
PubMed: 31755927
DOI: 10.1042/EBC20190038 -
Current Opinion in Plant Biology Aug 2022Cytosine is methylated in both CpG and non-CpG contexts (mCG and mCH, respectively) in plant genomes. Although mCG and mCH are almost independent in regard to their... (Review)
Review
Cytosine is methylated in both CpG and non-CpG contexts (mCG and mCH, respectively) in plant genomes. Although mCG and mCH are almost independent in regard to their "maintenance," recent studies uncovered crosstalk between them during their "establishment," which unexpectedly functions in both RNAi-dependent and -independent pathways. In addition, the importance of linker histone H1 and variants of histone H2A to DNA methylation dynamics is starting to be understood. We summarize these new aspects of mechanisms to generate DNA methylomes and discuss future prospects.
Topics: DNA Methylation; Epigenome
PubMed: 35724481
DOI: 10.1016/j.pbi.2022.102248 -
Clinical Epigenetics Jul 2019Peptides originating from different sources (endogenous, food derived, environmental, and synthetic) are able to influence different aspects of epigenetic regulation.... (Review)
Review
Peptides originating from different sources (endogenous, food derived, environmental, and synthetic) are able to influence different aspects of epigenetic regulation. Endogenous short peptides, resulting from proteolytic cleavage of proteins or upon translation of non-annotated out of frame transcripts, can block DNA methylation and hereby regulate gene expression. Peptides entering the body by digestion of food-related proteins can modulate DNA methylation and/or histone acetylation while environmental peptides, synthesized by bacteria, fungi, and marine sponges, mainly inhibit histone deacetylation. In addition, synthetic peptides that reverse or inhibit different epigenetic modifications of both histones and the DNA can be developed as well. Next to these DNA and histone modifications, peptides can also influence the expression of non-coding RNAs such as lncRNAs and the maturation of miRNAs.Seen the advantages over small molecules, the development of peptide therapeutics is an interesting approach to treat diseases with a strong epigenetic basis like cancer and Alzheimer's disease. To date, only a limited number of drugs with a proven epigenetic mechanism of action have been approved by the FDA of which two (romidepsin and nesiritide) are peptides. A large knowledge gap concerning epigenetic effects of peptides is present, and this class of molecules deserves more attention in the development as epigenetic modulators. In addition, none of the currently approved peptide drugs are under investigation for their potential effects on epigenetics, hampering drug repositioning of these peptides to other indications with an epigenetic etiology.
Topics: Acetylation; DNA Methylation; Epigenesis, Genetic; Histones; Humans; Peptides
PubMed: 31300053
DOI: 10.1186/s13148-019-0700-7 -
Essays in Biochemistry Oct 2020Cells encounter a multitude of external and internal stress-causing agents that can ultimately lead to DNA damage, mutations and disease. A cascade of signaling events... (Review)
Review
Cells encounter a multitude of external and internal stress-causing agents that can ultimately lead to DNA damage, mutations and disease. A cascade of signaling events counters these challenges to DNA, which is termed as the DNA damage response (DDR). The DDR preserves genome integrity by engaging appropriate repair pathways, while also coordinating cell cycle and/or apoptotic responses. Although many of the protein components in the DDR are identified, how chemical modifications to DNA impact the DDR is poorly understood. This review focuses on our current understanding of DNA methylation in maintaining genome integrity in mammalian cells. DNA methylation is a reversible epigenetic mark, which has been implicated in DNA damage signaling, repair and replication. Sites of DNA methylation can trigger mutations, which are drivers of human diseases including cancer. Indeed, alterations in DNA methylation are associated with increased susceptibility to tumorigenesis but whether this occurs through effects on the DDR, transcriptional responses or both is not entirely clear. Here, we also highlight epigenetic drugs currently in use as therapeutics that target DNA methylation pathways and discuss their effects in the context of the DDR. Finally, we pose unanswered questions regarding the interplay between DNA methylation, transcription and the DDR, positing the potential coordinated efforts of these pathways in genome integrity. While the impact of DNA methylation on gene regulation is widely understood, how this modification contributes to genome instability and mutations, either directly or indirectly, and the potential therapeutic opportunities in targeting DNA methylation pathways in cancer remain active areas of investigation.
Topics: Animals; DNA Methylation; Genome; Humans
PubMed: 32808652
DOI: 10.1042/EBC20200009