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Essays in Biochemistry Dec 2019Monoallelic gene expression occurs in diploid cells when only one of the two alleles of a gene is active. There are three main classes of genes that display monoallelic... (Review)
Review
Monoallelic gene expression occurs in diploid cells when only one of the two alleles of a gene is active. There are three main classes of genes that display monoallelic expression in mammalian genomes: (1) imprinted genes that are monoallelically expressed in a parent-of-origin dependent manner; (2) X-linked genes that undergo random X-chromosome inactivation in female cells; (3) random monoallelically expressed single and clustered genes located on autosomes. The heritability of monoallelic expression patterns during cell divisions implies that epigenetic mechanisms are involved in the cellular memory of these expression states. Among these, methylation of CpG sites on DNA is one of the best described modification to explain somatic inheritance. Here, we discuss the relevance of DNA methylation for the establishment and maintenance of monoallelic expression patterns among these three groups of genes, and how this is intrinsically linked to development and cellular states.
Topics: Alleles; Animals; DNA; DNA Methylation; Epigenesis, Genetic; Female; Gene Expression; Genomic Imprinting; Humans; X Chromosome Inactivation
PubMed: 31782494
DOI: 10.1042/EBC20190034 -
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 -
Philosophical Transactions of the Royal... May 2021Mollusca are the second largest and arguably most diverse phylum of the animal kingdom. This is in sharp contrast to our very limited knowledge concerning epigenetic...
Mollusca are the second largest and arguably most diverse phylum of the animal kingdom. This is in sharp contrast to our very limited knowledge concerning epigenetic mechanisms including DNA methylation in this invertebrate group. Here, we inferred DNA methylation patterns by analysing the normalized dinucleotide CG content in protein-coding sequences and identified DNA methyltransferases (DNMT1 and 3) in published transcriptomes and genomes of 140 species across all eight classes of molluscs. Given the evolutionary age and morphological diversity of molluscs, we expected to find evidence for diverse methylation patterns. Our inferences suggest that molluscs possess substantial levels of DNA methylation in gene bodies as a rule. Yet, we found deviations from this general picture with regard to (i) the CpG observed/expected distributions indicating a reduction in DNA methylation in certain groups and (ii) the completeness of the DNMT toolkit. Reductions were evident in Caudofoveata, Solenogastres, Polyplacophora, Monoplacophora, as well as Scaphopoda. Heterobranchia and Oegopsida were remarkable as they lacked DNMT3, usually responsible for de novo methylation, yet showed signs of DNA methylation. Our survey may serve as guidance for direct empirical analyses of DNA methylation in molluscs. This article is part of the Theo Murphy meeting issue 'Molluscan genomics: broad insights and future directions for a neglected phylum'.
Topics: Animals; DNA Methylation; Mollusca
PubMed: 33813896
DOI: 10.1098/rstb.2020.0166 -
Cell Reports Methods Nov 2022Researching the murine epigenome in disease models has been hampered by the lack of appropriate and cost-effective DNA methylation arrays. Here we perform a...
Researching the murine epigenome in disease models has been hampered by the lack of appropriate and cost-effective DNA methylation arrays. Here we perform a comprehensive, comparative analysis between the Mouse Methylation BeadChip (MMB) and reduced-representation bisulfite sequencing (RRBS) in two murine models of colorectal carcinogenesis. We evaluate the coverage, variability, and ability to identify differential DNA methylation of RRBS and MMB. We show that MMB is an effective tool for profiling the murine methylome that performs comparably with RRBS, identifying similar differentially methylated pathways. Although choice of technology is experiment dependent and will be predicated on the underlying biology being probed, these analyses provide insights into the relative strengths and weaknesses of each approach.
Topics: Animals; Mice; DNA Methylation; Sequence Analysis, DNA; Sulfites; Epigenome
PubMed: 36452869
DOI: 10.1016/j.crmeth.2022.100323 -
The Lancet. Healthy Longevity Feb 2023
Topics: DNA Methylation; Longevity
PubMed: 36738742
DOI: 10.1016/S2666-7568(23)00006-5 -
BioMed Research International 2022Endometrial cancer greatly threatens the health of female. Emerging evidences have demonstrated that DNA methylation and immune infiltration are involved in the...
BACKGROUND
Endometrial cancer greatly threatens the health of female. Emerging evidences have demonstrated that DNA methylation and immune infiltration are involved in the occurrence and development of endometrial cancer. However, the mechanism and prognostic biomarkers of endometrial cancer are still unclear. In this study, we assess DNA methylation and immune infiltration via bioinformatic analysis.
METHODS
The latest RNA-Seq, DNA methylation data, and clinical data related to endometrial cancer were downloaded from the UCSC Xena dataset. The methylation-driven genes were selected, and then the risk score was obtained using "MethylMix" and "corrplot" R packages. The connection between methylated genes and the expression of screened driven genes were explored using "survminer" and "beeswarm" packages, respectively. Finally, the role of in immune infiltration was analyzed using "CIBERSORT" package.
RESULTS
In this study, 179 upregulated genes, and 311 downregulated genes were identified and found to be related to extracellular matrix organization, cell-cell junctions, and cell adhesion molecular binding. The methylation-driven gene was selected, and patients classified to the hypomethylation and high expression group displayed poor prognosis. The gene exhibited highest correlation coefficient between methylation and expression. More importantly, the hypomethylation of promoter of led to its high expression, thereby induce tumor development by inhibiting CD8+ T cell infiltration.
CONCLUSIONS
Overall, our study was the first to reveal the mechanism of endometrial cancer by assessing DNA methylation and immune infiltration via integrated bioinformatic analysis. In addition, we found a pivotal prognostic biomarker for the disease. Our study provides potential targets for the diagnosis and prognosis of endometrial cancer in the future.
Topics: Computational Biology; DNA Methylation; Endometrial Neoplasms; Female; Gene Expression Regulation, Neoplastic; Humans; Prognosis
PubMed: 35774278
DOI: 10.1155/2022/5119411 -
British Journal of Pharmacology Jun 2015One of the hallmarks of cancer is aberrant DNA methylation, which is associated with abnormal gene expression. Both hypermethylation and silencing of tumour suppressor... (Review)
Review
One of the hallmarks of cancer is aberrant DNA methylation, which is associated with abnormal gene expression. Both hypermethylation and silencing of tumour suppressor genes as well as hypomethylation and activation of prometastatic genes are characteristic of cancer cells. As DNA methylation is reversible, DNA methylation inhibitors were tested as anticancer drugs with the idea that such agents would demethylate and reactivate tumour suppressor genes. Two cytosine analogues, 5-azacytidine (Vidaza) and 5-aza-2'-deoxycytidine, were approved by the Food and Drug Administration as antitumour agents in 2004 and 2006 respectively. However, these agents might cause activation of a panel of prometastatic genes in addition to activating tumour suppressor genes, which might lead to increased metastasis. This poses the challenge of how to target tumour suppressor genes and block cancer growth with DNA-demethylating drugs while avoiding the activation of prometastatic genes and precluding the morbidity of cancer metastasis. This paper reviews current progress in using DNA methylation inhibitors in cancer therapy and the potential promise and challenges ahead.
Topics: Antimetabolites, Antineoplastic; Azacitidine; DNA Methylation; Decitabine; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms
PubMed: 25134627
DOI: 10.1111/bph.12885 -
International Journal of Molecular... Dec 2020Osteoporosis is a complex multifactorial condition of the musculoskeletal system. Osteoporosis and osteoporotic vertebral fracture (OVF) are associated with high medical... (Review)
Review
Osteoporosis is a complex multifactorial condition of the musculoskeletal system. Osteoporosis and osteoporotic vertebral fracture (OVF) are associated with high medical costs and can lead to poor quality of life. Genetic factors are important in determining bone mass and structure, as well as any predisposition for bone degradation and OVF. However, genetic factors are not enough to explain osteoporosis development and OVF occurrence. Epigenetics describes a mechanism for controlling gene expression and cellular processes without altering DNA sequences. The main mechanisms in epigenetics are DNA methylation, histone modifications, and non-coding RNAs (ncRNAs). Recently, alterations in epigenetic mechanisms and their activity have been associated with osteoporosis and OVF. Here, we review emerging evidence that epigenetics contributes to the machinery that can alter DNA structure, gene expression, and cellular differentiation during physiological and pathological bone remodeling. A progressive understanding of normal bone metabolism and the role of epigenetic mechanisms in multifactorial osteopathy can help us better understand the etiology of the disease and convert this information into clinical practice. A deep understanding of these mechanisms will help in properly coordinating future individual treatments of osteoporosis and OVF.
Topics: DNA Methylation; Epigenesis, Genetic; Epigenomics; Fractures, Bone; Humans; Osteoporosis; Osteoporotic Fractures; Spinal Fractures
PubMed: 33322579
DOI: 10.3390/ijms21249455 -
International Journal of Molecular... Dec 2018DNA methylation is a vital modification process in the control of genetic information, which contributes to the epigenetics by regulating gene expression without... (Review)
Review
DNA methylation is a vital modification process in the control of genetic information, which contributes to the epigenetics by regulating gene expression without changing the DNA sequence. Abnormal DNA methylation-both hypomethylation and hypermethylation-has been associated with improper gene expression, leading to several disorders. Two types of risk factors can alter the epigenetic regulation of methylation pathways: genetic factors and modifiable factors. Nutrition is one of the strongest modifiable factors, which plays a direct role in DNA methylation pathways. Large numbers of studies have investigated the effects of nutrition on DNA methylation pathways, but relatively few have focused on the biochemical mechanisms. Understanding the biological mechanisms is essential for clarifying how nutrients function in epigenetics. It is believed that nutrition affects the epigenetic regulations of DNA methylation in several possible epigenetic pathways: mainly, by altering the substrates and cofactors that are necessary for proper DNA methylation; additionally, by changing the activity of enzymes regulating the one-carbon cycle; and, lastly, through there being an epigenetic role in several possible mechanisms related to DNA demethylation activity. The aim of this article is to review the potential underlying biochemical mechanisms that are related to diet modifications in DNA methylation and demethylation.
Topics: Animals; Carbon Cycle; DNA Methylation; DNA-Cytosine Methylases; Diet; Epigenesis, Genetic; Gene Expression Regulation; Humans
PubMed: 30558203
DOI: 10.3390/ijms19124055 -
Clinical Epigenetics Dec 2021Socioeconomic position (SEP) is a major determinant of health across the life course. Yet, little is known about the biological mechanisms explaining this relationship.... (Review)
Review
BACKGROUND
Socioeconomic position (SEP) is a major determinant of health across the life course. Yet, little is known about the biological mechanisms explaining this relationship. One possibility widely pursued in the scientific literature is that SEP becomes biologically embedded through epigenetic processes such as DNA methylation (DNAm), wherein the socioeconomic environment causes no alteration in the DNA sequence but modifies gene activity in ways that shape health.
METHODS
To understand the evidence supporting a potential SEP-DNAm link, we performed a scoping review of published empirical findings on the association between SEP assessed from prenatal development to adulthood and DNAm measured across the life course, with an emphasis on exploring how the developmental timing, duration, and type of SEP exposure influenced DNAm.
RESULTS
Across the 37 identified studies, we found that: (1) SEP-related DNAm signatures varied across the timing, duration, and type of SEP indicator; (2) however, longitudinal studies examining repeated SEP and DNAm measures are generally lacking; and (3) prior studies are conceptually and methodologically diverse, limiting the interpretability of findings across studies with respect to these three SEP features.
CONCLUSIONS
Given the complex relationship between SEP and DNAm across the lifespan, these findings underscore the importance of analyzing SEP features, including timing, duration, and type. To guide future research, we highlight additional research gaps and propose four recommendations to further unravel the relationship between SEP and DNAm.
Topics: Correlation of Data; DNA Methylation; Humans; Social Class
PubMed: 34906220
DOI: 10.1186/s13148-021-01189-0