1 2833 65 FOLATE AND DNA METHYLATION: A REVIEW OF MOLECULAR MECHANISMS AND THE EVIDENCE FOR FOLATE'S ROLE. DNA METHYLATION IS AN EPIGENETIC MODIFICATION CRITICAL TO NORMAL GENOME REGULATION AND DEVELOPMENT. THE VITAMIN FOLATE IS A KEY SOURCE OF THE ONE CARBON GROUP USED TO METHYLATE DNA. BECAUSE NORMAL MAMMALIAN DEVELOPMENT IS DEPENDENT ON DNA METHYLATION, THERE IS ENORMOUS INTEREST IN ASSESSING THE POTENTIAL FOR CHANGES IN FOLATE INTAKE TO MODULATE DNA METHYLATION BOTH AS A BIOMARKER FOR FOLATE STATUS AND AS A MECHANISTIC LINK TO DEVELOPMENTAL DISORDERS AND CHRONIC DISEASES INCLUDING CANCER. THIS REVIEW HIGHLIGHTS THE ROLE OF DNA METHYLATION IN NORMAL GENOME FUNCTION, HOW IT CAN BE ALTERED, AND THE EVIDENCE OF THE ROLE OF FOLATE/FOLIC ACID IN THESE PROCESSES. 2012 2 315 27 ALCOHOL, DNA METHYLATION, AND CANCER. CANCER IS ONE OF THE MOST SIGNIFICANT DISEASES ASSOCIATED WITH CHRONIC ALCOHOL CONSUMPTION, AND CHRONIC DRINKING IS A STRONG RISK FACTOR FOR CANCER, PARTICULARLY OF THE UPPER AERODIGESTIVE TRACT, LIVER, COLORECTUM, AND BREAST. SEVERAL FACTORS CONTRIBUTE TO ALCOHOL-INDUCED CANCER DEVELOPMENT (I.E., CARCINOGENESIS), INCLUDING THE ACTIONS OF ACETALDEHYDE, THE FIRST AND PRIMARY METABOLITE OF ETHANOL, AND OXIDATIVE STRESS. HOWEVER, INCREASING EVIDENCE SUGGESTS THAT ABERRANT PATTERNS OF DNA METHYLATION, AN IMPORTANT EPIGENETIC MECHANISM OF TRANSCRIPTIONAL CONTROL, ALSO COULD BE PART OF THE PATHOGENETIC MECHANISMS THAT LEAD TO ALCOHOL-INDUCED CANCER DEVELOPMENT. THE EFFECTS OF ALCOHOL ON GLOBAL AND LOCAL DNA METHYLATION PATTERNS LIKELY ARE MEDIATED BY ITS ABILITY TO INTERFERE WITH THE AVAILABILITY OF THE PRINCIPAL BIOLOGICAL METHYL DONOR, S-ADENOSYLMETHIONINE (SAME), AS WELL AS PATHWAYS RELATED TO IT. SEVERAL MECHANISMS MAY MEDIATE THE EFFECTS OF ALCOHOL ON DNA METHYLATION, INCLUDING REDUCED FOLATE LEVELS AND INHIBITION OF KEY ENZYMES IN ONE-CARBON METABOLISM THAT ULTIMATELY LEAD TO LOWER SAME LEVELS, AS WELL AS INHIBITION OF ACTIVITY AND EXPRESSION OF ENZYMES INVOLVED IN DNA METHYLATION (I.E., DNA METHYLTRANSFERASES). FINALLY, VARIATIONS (I.E., POLYMORPHISMS) OF SEVERAL GENES INVOLVED IN ONE-CARBON METABOLISM ALSO MODULATE THE RISK OF ALCOHOL-ASSOCIATED CARCINOGENESIS. 2013 3 1912 26 ENVIRONMENT, DIET AND CPG ISLAND METHYLATION: EPIGENETIC SIGNALS IN GASTROINTESTINAL NEOPLASIA. THE EPITHELIAL SURFACES OF THE MAMMALIAN ALIMENTARY TRACT ARE CHARACTERISED BY VERY HIGH RATES OF CELL PROLIFERATION AND DNA SYNTHESIS, AND IN HUMANS THEY ARE HIGHLY SUSCEPTIBLE TO CANCER. THE ROLE OF SOMATIC MUTATIONS AS DRIVERS OF CARCINOGENESIS IN THE ALIMENTARY TRACT IS WELL ESTABLISHED, BUT THE IMPORTANCE OF GENE SILENCING BY EPIGENETIC MECHANISMS IS INCREASINGLY RECOGNISED. METHYLATION OF CPG ISLANDS IS AN IMPORTANT COMPONENT OF THE EPIGENETIC CODE THAT REGULATES GENE EXPRESSION DURING DEVELOPMENT AND NORMAL CELLULAR DIFFERENTIATION, AND A NUMBER OF GENES ARE WELL KNOWN TO BECOME ABNORMALLY METHYLATED DURING THE DEVELOPMENT OF TUMOURS OF THE OESOPHAGUS, STOMACH AND COLORECTUM. ABERRANT PATTERNS OF DNA METHYLATION DEVELOP AS A RESULT OF PATHOLOGICAL PROCESSES SUCH AS CHRONIC INFLAMMATION, AND IN RESPONSE TO VARIOUS DIETARY FACTORS, INCLUDING IMBALANCES IN THE SUPPLY OF METHYL DONORS, PARTICULARLY FOLATES, AND EXPOSURE TO DNA METHYLTRANSFERASE INHIBITORS, WHICH INCLUDE POLYPHENOLS AND POSSIBLY ISOTHIOCYANATES FROM PLANT FOODS. HOWEVER THE IMPORTANCE OF THESE ENVIRONMENTAL INTERACTIONS IN HUMAN HEALTH AND DISEASE REMAINS TO BE ESTABLISHED. RECENT MOVES TO MODIFY THE EXPOSURE OF HUMAN POPULATIONS TO FOLATE, BY MANDATORY SUPPLEMENTATION OF CEREAL FOODS, EMPHASISE THE IMPORTANCE OF UNDERSTANDING THE SUSCEPTIBILITY OF THE HUMAN EPIGENOME TO DIETARY AND OTHER ENVIRONMENTAL EFFECTS. 2008 4 318 31 ALCOHOL-INDUCED EPIGENETIC CHANGES IN CANCER. CHRONIC, HEAVY ALCOHOL CONSUMPTION IS ASSOCIATED WITH SERIOUS NEGATIVE HEALTH EFFECTS, INCLUDING THE DEVELOPMENT OF SEVERAL CANCER TYPES. ONE OF THE PATHWAYS AFFECTED BY ALCOHOL TOXICITY IS THE ONE-CARBON METABOLISM. THE ALCOHOL-INDUCED IMPAIRMENT OF THIS METABOLIC PATHWAY RESULTS IN EPIGENETIC CHANGES ASSOCIATED WITH CANCER DEVELOPMENT. THESE EPIGENETIC CHANGES ARE INDUCED BY FOLATE DEFICIENCY AND BY PRODUCTS OF THE ETHANOL METABOLISM. THE CHANGES INDUCED BY LONG-TERM HEAVY ETHANOL CONSUMPTION RESULT IN ELEVATIONS OF HOMOCYSTEINE AND S-ADENOSYL-HOMOCYSTEINE (SAH) AND REDUCTIONS IN S-ADENOSYLMETHIONINE (SAM) AND ANTIOXIDANT GLUTATHIONE (GSH) LEVELS, LEADING TO ABNORMAL PROMOTER GENE HYPERMETHYLATION, GLOBAL HYPOMETHYLATION, AND METABOLIC INSUFFICIENCY OF ANTIOXIDANT DEFENSE MECHANISMS. IN ADDITION, REACTIVE OXYGEN SPECIES (ROS) GENERATED DURING THE ETHANOL METABOLISM INDUCE ALTERATIONS IN DNA METHYLATION PATTERNS THAT PLAY A CRITICAL ROLE IN CANCER DEVELOPMENT. SPECIFIC EPIGENETIC CHANGES IN ESOPHAGEAL, HEPATIC, AND COLORECTAL CANCERS HAVE BEEN DETECTED IN BLOOD SAMPLES AND PROPOSED TO BE USED CLINICALLY AS EPIGENETIC BIOMARKERS FOR DIAGNOSIS AND PROGNOSIS OF THESE CANCERS. ALSO, GENETIC VARIANTS OF GENES INVOLVED IN ONE-CARBON METABOLISM AND ETHANOL METABOLISM WERE FOUND TO MODULATE THE RELATIONSHIP BETWEEN ALCOHOL-INDUCED EPIGENETIC CHANGES AND CANCER RISK. FURTHERMORE, ALCOHOL METABOLISM PRODUCTS HAVE BEEN ASSOCIATED WITH AN INCREASE IN NADH LEVELS, WHICH LEAD TO HISTONE MODIFICATIONS AND CHANGES IN GENE EXPRESSION THAT IN TURN INFLUENCE CANCER SUSCEPTIBILITY. CHRONIC EXCESSIVE USE OF ALCOHOL ALSO AFFECTS SELECTED MEMBERS OF THE FAMILY OF MICRORNAS, AND AS MIRNAS COULD ACT AS EPIGENETIC REGULATORS, THIS MAY PLAY AN IMPORTANT ROLE IN CARCINOGENESIS. IN CONCLUSION, TARGETING ALCOHOL-INDUCED EPIGENETIC CHANGES IN SEVERAL CANCER TYPES COULD MAKE AVAILABLE CLINICAL TOOLS FOR THE DIAGNOSIS, PROGNOSIS, AND TREATMENT OF THESE CANCERS, WITH AN IMPORTANT ROLE IN PRECISION MEDICINE. 2018 5 4217 27 METHYL DONOR NUTRIENTS IN CHRONIC KIDNEY DISEASE: IMPACT ON THE EPIGENETIC LANDSCAPE. EPIGENETIC ALTERATIONS, SUCH AS THOSE LINKED TO DNA METHYLATION, MAY POTENTIALLY PROVIDE MOLECULAR EXPLANATIONS FOR COMPLICATIONS ASSOCIATED WITH ALTERED GENE EXPRESSION IN ILLNESSES, SUCH AS CHRONIC KIDNEY DISEASE (CKD). ALTHOUGH BOTH DNA HYPO- AND HYPERMETHYLATION HAVE BEEN OBSERVED IN THE UREMIC MILIEU, THIS REMAINS ONLY A SINGLE ASPECT OF THE EPIGENETIC LANDSCAPE AND, THUS, OF ANY BIOCHEMICAL DYSREGULATION ASSOCIATED WITH CKD. NEVERTHELESS, THE ROLE OF UREMIA-PROMOTING ALTERATIONS ON THE EPIGENETIC LANDSCAPE REGULATING GENE EXPRESSION IS STILL A NOVEL AND SCARCELY STUDIED FIELD. ALTHOUGH FEW STUDIES HAVE ACTUALLY REPORTED ALTERATIONS OF DNA METHYLATION VIA METHYL DONOR NUTRIENT INTAKE, EMERGING EVIDENCE INDICATES THAT NUTRITIONAL MODIFICATION OF THE MICROBIOME CAN AFFECT ONE-CARBON METABOLISM AND THE CAPACITY TO METHYLATE THE GENOME IN CKD. IN THIS REVIEW, WE DISCUSS THE NUTRITIONAL MODIFICATIONS THAT MAY AFFECT ONE-CARBON METABOLISM AND THE POSSIBLE IMPACT OF METHYL DONOR NUTRIENTS ON THE MICROBIOME, CKD, AND ITS PHENOTYPE. 2019 6 5067 28 PHYSICAL ACTIVITY AND DNA METHYLATION IN HUMANS. PHYSICAL ACTIVITY IS A STRONG STIMULUS INFLUENCING THE OVERALL PHYSIOLOGY OF THE HUMAN BODY. EXERCISES LEAD TO BIOCHEMICAL CHANGES IN VARIOUS TISSUES AND EXERT AN IMPACT ON GENE EXPRESSION. EXERCISE-INDUCED CHANGES IN GENE EXPRESSION MAY BE MEDIATED BY EPIGENETIC MODIFICATIONS, WHICH REARRANGE THE CHROMATIN STRUCTURE AND THEREFORE MODULATE ITS ACCESSIBILITY FOR TRANSCRIPTION FACTORS. ONE OF SUCH EPIGENETIC MARK IS DNA METHYLATION THAT INVOLVES AN ATTACHMENT OF A METHYL GROUP TO THE FIFTH CARBON OF CYTOSINE RESIDUE PRESENT IN CG DINUCLEOTIDES (CPG). DNA METHYLATION IS CATALYZED BY A FAMILY OF DNA METHYLTRANSFERASES. THIS REVERSIBLE DNA MODIFICATION RESULTS IN THE RECRUITMENT OF PROTEINS CONTAINING METHYL BINDING DOMAIN AND FURTHER TRANSCRIPTIONAL CO-REPRESSORS LEADING TO THE SILENCING OF GENE EXPRESSION. THE ACCUMULATION OF CPG DINUCLEOTIDES, REFERRED AS CPG ISLANDS, OCCURS AT THE PROMOTER REGIONS IN A GREAT MAJORITY OF HUMAN GENES. THEREFORE, CHANGES IN DNA METHYLATION PROFILE AFFECT THE TRANSCRIPTION OF MULTIPLE GENES. A GROWING BODY OF EVIDENCE INDICATES THAT EXERCISE TRAINING MODULATES DNA METHYLATION IN MUSCLES AND ADIPOSE TISSUE. SOME OF THESE EPIGENETIC MARKERS WERE ASSOCIATED WITH A REDUCED RISK OF CHRONIC DISEASES. THIS REVIEW SUMMARIZES THE CURRENT KNOWLEDGE ABOUT THE INFLUENCE OF PHYSICAL ACTIVITY ON THE DNA METHYLATION STATUS IN HUMANS. 2021 7 6771 25 [ACQUIRED DISORDERS AND EPIGENETICS]. EPIGENETIC MODIFICATIONS, INVOLVING DNA METHYLATION AND HISTONE MODIFICATIONS, ARE MAINTAINED UPON SOMATIC CELL REPLICATION, AND ARE FUNDAMENTAL MECHANISMS FOR CELLULAR MEMORY. DNA METHYLATION OF PROMOTER CPG ISLANDS OF TUMOR-SUPPRESSOR GENES CAN SILENCE THEIR DOWNSTREAM GENES, AND CAN BE CAUSALLY INVOLVED IN CANCER DEVELOPMENT AND PROGRESSION. SINCE THIS EFFECT IS THE SAME WITH THAT OF INACTIVATING MUTATIONS, THE NATURES OF DNA METHYLATION WERE ONCE CONSIDERED TO BE SIMILAR TO MUTATIONS. HOWEVER, RECENTLY, IT WAS REVEALED THAT A LARGE NUMBER OF EPIGENETIC ALTERATIONS ARE PRESENT IN A SINGLE CANCER CELL, THAT A LARGE NUMBER OF CELLS HAVE AN EPIGENETIC ALTERATION OF A SPECIFIC GENE IN NON-CANCEROUS, THUS POLYCLONAL, TISSUES, THAT GENE SPECIFICITY IN METHYLATION INDUCTION IS PRESENT ACCORDING TO TISSUE TYPES AND INDUCERS, AND THAT CHRONIC INFLAMMATION IS DEEPLY INVOLVED IN METHYLATION INDUCTION. THESE FACTS SUGGEST THAT EPIGENETIC ALTERATIONS OF KEY GENES INVOLVED IN ACQUIRED CHRONIC DISORDERS CAN BE PRESENT IN A SIGNIFICANT FRACTION OF CELLS IN A TISSUE, AND THUS CAN IMPAIR THE FUNCTION OF THE TISSUE. ASSOCIATIONS BETWEEN EPIGENETIC ALTERATIONS AND BEHAVIOR, MEMORY, MENTAL DISORDERS, NEUROLOGICAL DISORDERS, METABOLIC DISORDERS, ALLERGY, AUTOIMMUNE DISORDERS, AND OTHER DISORDERS HAVE BEEN REPORTED. FURTHER RESEARCH IN THE FIELD IS NECESSARY TO CLARIFY THE CAUSAL ROLES OF THESE EPIGENETIC ALTERATIONS IN DISEASE DEVELOPMENT, AND TO APPLY THE FINDINGS TO NEW STRATEGIES OF DISEASE PREVENTION, DIAGNOSIS, AND TREATMENT. 2010 8 6715 30 VITAMIN A AND THE EPIGENOME. THE EPIGENETIC PHENOMENA REFER TO HERITABLE CHANGES IN GENE EXPRESSION OTHER THAN THOSE IN THE DNA SEQUENCE, SUCH AS DNA METHYLATION AND HISTONE MODIFICATIONS. MAJOR RESEARCH PROGRESS IN THE LAST FEW YEARS HAS PROVIDED FURTHER PROOF THAT ENVIRONMENTAL FACTORS, INCLUDING DIET AND NUTRITION, CAN INFLUENCE PHYSIOLOGIC AND PATHOLOGIC PROCESSES THROUGH EPIGENETIC ALTERATIONS, WHICH IN TURN INFLUENCE GENE EXPRESSION. THIS INFLUENCE IS TERMED NUTRITIONAL EPIGENETICS, AND ONE PROMINENT EXAMPLE IS THE REGULATION OF GENE TRANSCRIPTION BY VITAMIN A THROUGH INTERACTION TO ITS NUCLEAR RECEPTOR. VITAMIN A IS CRITICAL THROUGHOUT LIFE. TOGETHER WITH ITS DERIVATIVES, IT REGULATES DIVERSE PROCESSES INCLUDING REPRODUCTION, EMBRYOGENESIS, VISION, GROWTH, CELLULAR DIFFERENTIATION AND PROLIFERATION, MAINTENANCE OF EPITHELIAL CELLULAR INTEGRITY AND IMMUNE FUNCTION. HERE WE REVIEW THE EPIGENETIC ROLE OF VITAMIN A IN CANCER, STEM CELLS DIFFERENTIATION, PROLIFERATION, AND IMMUNITY. THE DATA PRESENTED HERE SHOW THAT RETINOIC ACID IS A POTENT AGENT CAPABLE OF INDUCING ALTERATIONS IN EPIGENETIC MODIFICATIONS THAT PRODUCE VARIOUS EFFECTS ON THE PHENOTYPE. MEDICAL BENEFITS OF VITAMIN A AS AN EPIGENETIC MODULATOR, ESPECIALLY WITH RESPECT TO ITS CHRONIC USE AS NUTRITIONAL SUPPLEMENT, SHOULD RELY ON OUR FURTHER UNDERSTANDING OF ITS EPIGENETIC EFFECTS DURING HEALTH AND DISEASE, AS WELL AS THROUGH DIFFERENT GENERATIONS. 2017 9 2541 23 EPIGENETICS IN KIDNEY DEVELOPMENT AND RENAL DISEASE. THE STUDY OF EPIGENETICS IS INTIMATELY LINKED AND INSEPARABLE FROM DEVELOPMENTAL BIOLOGY. MANY OF THE GENES THAT IMPRINT EPIGENETIC INFORMATION ON CHROMATIN FUNCTION DURING THE SPECIFICATION OF CELL LINEAGES IN THE DEVELOPING EMBRYO. THESE INCLUDE THE HISTONE METHYLTRANSFERASES AND THEIR COFACTORS OF THE POLYCOMB AND TRITHORAX GENE FAMILIES. HOW HISTONE METHYLATION IS ESTABLISHED AND WHAT REGULATES THE TISSUE AND LOCUS SPECIFICITY OF HISTONE METHYLATION IS AN EMERGING AREA OF RESEARCH. THE EMBRYONIC KIDNEY IS USED AS A MODEL TO UNDERSTAND HOW DNA-BINDING PROTEINS CAN SPECIFY CELL LINEAGES AND HOW SUCH PROTEINS INTERACT DIRECTLY WITH THE HISTONE METHYLATION MACHINERY TO GENERATE A UNIQUE EPIGENOME FOR PARTICULAR TISSUES AND CELL TYPES. IN ADULT TISSUES, HISTONE METHYLATION MARKS MUST BE MAINTAINED FOR NORMAL GENE EXPRESSION PATTERNS. IN CHRONIC AND ACUTE RENAL DISEASE, EPIGENETIC MARKS ARE BEING CHARACTERIZED AND CORRELATED WITH THE ESTABLISHMENT OF METABOLIC MEMORY, IN PART TO EXPLAIN THE PERSISTENCE OF PATHOLOGIES EVEN WHEN OPTIMAL TREATMENT MODALITIES ARE USED. THUS, THE STATE OF THE EPIGENOME IN ADULT CELLS MUST BE CONSIDERED WHEN ATTEMPTING TO ALLEVIATE OR ALTER GENE EXPRESSION PATTERNS IN DISEASE. 2015 10 2523 28 EPIGENETICS AND THE TRANSITION FROM ACUTE TO CHRONIC PAIN. OBJECTIVE: THE OBJECTIVE OF THIS STUDY WAS TO REVIEW THE EPIGENETIC MODIFICATIONS INVOLVED IN THE TRANSITION FROM ACUTE TO CHRONIC PAIN AND TO IDENTIFY POTENTIAL TARGETS FOR THE DEVELOPMENT OF NOVEL, INDIVIDUALIZED PAIN THERAPEUTICS. BACKGROUND: EPIGENETICS IS THE STUDY OF HERITABLE MODIFICATIONS IN GENE EXPRESSION AND PHENOTYPE THAT DO NOT REQUIRE A CHANGE IN GENETIC SEQUENCE TO MANIFEST THEIR EFFECTS. ENVIRONMENTAL TOXINS, MEDICATIONS, DIET, AND PSYCHOLOGICAL STRESSES CAN ALTER EPIGENETIC PROCESSES SUCH AS DNA METHYLATION, HISTONE ACETYLATION, AND RNA INTERFERENCE. AS EPIGENETIC MODIFICATIONS POTENTIALLY PLAY AN IMPORTANT ROLE IN INFLAMMATORY CYTOKINE METABOLISM, STEROID RESPONSIVENESS, AND OPIOID SENSITIVITY, THEY ARE LIKELY KEY FACTORS IN THE DEVELOPMENT OF CHRONIC PAIN. ALTHOUGH OUR KNOWLEDGE OF THE HUMAN GENETIC CODE AND DISEASE-ASSOCIATED POLYMORPHISMS HAS GROWN SIGNIFICANTLY IN THE PAST DECADE, WE HAVE NOT YET BEEN ABLE TO ELUCIDATE THE MECHANISMS THAT LEAD TO THE DEVELOPMENT OF PERSISTENT PAIN AFTER NERVE INJURY OR SURGERY. DESIGN: THIS IS A FOCUSED LITERATURE REVIEW OF EPIGENETIC SCIENCE AND ITS RELATIONSHIP TO CHRONIC PAIN. RESULTS: SIGNIFICANT LABORATORY AND CLINICAL DATA SUPPORT THE NOTION THAT EPIGENETIC MODIFICATIONS ARE AFFECTED BY THE ENVIRONMENT AND LEAD TO DIFFERENTIAL GENE EXPRESSION. SIMILAR TO MECHANISMS INVOLVED IN THE DEVELOPMENT OF CANCER, NEURODEGENERATIVE DISEASE, AND INFLAMMATORY DISORDERS, THE LITERATURE ENDORSES AN IMPORTANT POTENTIAL ROLE FOR EPIGENETICS IN CHRONIC PAIN. CONCLUSIONS: EPIGENETIC ANALYSIS MAY IDENTIFY MECHANISMS CRITICAL TO THE DEVELOPMENT OF CHRONIC PAIN AFTER INJURY, AND MAY PROVIDE NEW PATHWAYS AND TARGET MECHANISMS FOR FUTURE DRUG DEVELOPMENT AND INDIVIDUALIZED MEDICINE. 2012 11 462 28 ARE ALTERATIONS IN DNA METHYLATION RELATED TO CKD DEVELOPMENT? THE MODIFICATIONS IN GENOMIC DNA METHYLATION ARE INVOLVED IN THE REGULATION OF NORMAL AND PATHOLOGICAL CELLULAR PROCESSES. THE EPIGENETIC REGULATION STIMULATES BIOLOGICAL PLASTICITY AS AN ADAPTIVE RESPONSE TO VARIATIONS IN ENVIRONMENTAL FACTORS. THE ROLE OF EPIGENETIC CHANGES IS VITAL FOR THE DEVELOPMENT OF SOME DISEASES, INCLUDING ATHEROGENESIS, CANCERS, AND CHRONIC KIDNEY DISEASE (CKD). THE RESULTS OF STUDIES PRESENTED IN THIS REVIEW HAVE SUGGESTED THAT ALTERED DNA METHYLATION CAN MODULATE THE EXPRESSION OF PRO-INFLAMMATORY AND PRO-FIBROTIC GENES, AS WELL THOSE ESSENTIAL FOR KIDNEY DEVELOPMENT AND FUNCTION, THUS STIMULATING RENAL DISEASE PROGRESSION. ABNORMALLY INCREASED HOMOCYSTEINE, HYPOXIA, AND INFLAMMATION HAVE BEEN SUGGESTED TO ALTER EPIGENETIC REGULATION OF GENE EXPRESSION IN CKD. STUDIES OF RENAL SAMPLES HAVE DEMONSTRATED THE RELATIONSHIP BETWEEN VARIATIONS IN DNA METHYLATION AND FIBROSIS AND VARIATIONS IN ESTIMATED GLOMERULAR FILTRATION RATE (EGFR) IN HUMAN CKD. THE UNRAVELLING OF THE GENETIC-EPIGENETIC PROFILE WOULD ENHANCE OUR UNDERSTANDING OF PROCESSES UNDERLYING THE DEVELOPMENT OF CKD. THE UNDERSTANDING OF MULTIFACETED RELATIONSHIP BETWEEN DNA METHYLATION, GENES EXPRESSION, AND DISEASE DEVELOPMENT AND PROGRESSION COULD IMPROVE THE ABILITY TO IDENTIFY INDIVIDUALS AT RISK OF CKD AND ENABLE THE CHOICE OF APPROPRIATE DISEASE MANAGEMENT. 2022 12 6809 24 [EPIGENETICS IN INFLAMMATORY SYSTEMIC DISEASES]. IN ADDITION TO ANALYSIS OF THE GENETIC CODE, IN RECENT YEARS MORE AND MORE STUDIES HAVE CONCENTRATED ON CHANGES IN THE EPIGENETIC CODE. EPIGENETIC MECHANISMS DETERMINE WHICH GENES IN A CELL ARE TRANSCRIBED AND THUS FORM THE PHENOTYPE OF A CELL. THE EPIGENETIC CODE CAN BE CHANGED BY ENVIRONMENTAL INFLUENCES, WHICH ALLOWS CELLS TO ADAPT TO LONGSTANDING CHANGES IN THE ENVIRONMENT. THEREFORE, IT IS FEASIBLE TO ASSUME THAT EPIGENETIC CHANGES ARE THE MOLECULAR BASIS FOR LONG-TERM EFFECTS OF THE ENVIRONMENT ON DISEASE DEVELOPMENT. IN PARTICULAR IN TUMORS AND CHRONIC INFLAMMATORY DISEASES EPIGENETIC CHANGES WERE FOUND TO CORRELATE WITH DISEASE SEVERITY AND PROGRESSION. KNOWLEDGE ABOUT THESE EPIGENETIC CHANGES MIGHT HELP THAT EPIGENETIC MODIFICATIONS CAN BE USED IN THE FUTURE AS BIOMARKERS, PROGNOSTIC FACTORS AND THERAPEUTIC TARGETS. 2014 13 712 26 CADMIUM AND ITS EPIGENETIC EFFECTS. CADMIUM (CD) IS A TOXIC, NONESSENTIAL TRANSITION METAL AND CONTRIBUTES A HEALTH RISK TO HUMANS, INCLUDING VARIOUS CANCERS AND CARDIOVASCULAR DISEASES; HOWEVER, UNDERLYING MOLECULAR MECHANISMS REMAIN LARGELY UNKNOWN. CELLS TRANSMIT INFORMATION TO THE NEXT GENERATION VIA TWO DISTINCT WAYS: GENETIC AND EPIGENETIC. CHEMICAL MODIFICATIONS TO DNA OR HISTONE THAT ALTERS THE STRUCTURE OF CHROMATIN WITHOUT CHANGE OF DNA NUCLEOTIDE SEQUENCE ARE KNOWN AS EPIGENETICS. THESE HERITABLE EPIGENETIC CHANGES INCLUDE DNA METHYLATION, POST-TRANSLATIONAL MODIFICATIONS OF HISTONE TAILS (ACETYLATION, METHYLATION, PHOSPHORYLATION, ETC), AND HIGHER ORDER PACKAGING OF DNA AROUND NUCLEOSOMES. APART FROM DNA METHYLTRANSFERASES, HISTONE MODIFICATION ENZYMES SUCH AS HISTONE ACETYLTRANSFERASE, HISTONE DEACETYLASE, AND METHYLTRANSFERASE, AND MICRORNAS (MIRNAS) ALL INVOLVE IN THESE EPIGENETIC CHANGES. RECENT STUDIES INDICATE THAT CD IS ABLE TO INDUCE VARIOUS EPIGENETIC CHANGES IN PLANT AND MAMMALIAN CELLS IN VITRO AND IN VIVO. SINCE ABERRANT EPIGENETICS PLAYS A CRITICAL ROLE IN THE DEVELOPMENT OF VARIOUS CANCERS AND CHRONIC DISEASES, CD MAY CAUSE THE ABOVE-MENTIONED PATHOGENIC RISKS VIA EPIGENETIC MECHANISMS. HERE WE REVIEW THE IN VITRO AND IN VIVO EVIDENCE OF EPIGENETIC EFFECTS OF CD. THE AVAILABLE FINDINGS INDICATE THAT EPIGENETICS OCCURRED IN ASSOCIATION WITH CD INDUCTION OF MALIGNANT TRANSFORMATION OF CELLS AND PATHOLOGICAL PROLIFERATION OF TISSUES, SUGGESTING THAT EPIGENETIC EFFECTS MAY PLAY A ROLE IN CD TOXIC, PARTICULARLY CARCINOGENIC EFFECTS. THE FUTURE OF ENVIRONMENTAL EPIGENOMIC RESEARCH ON CD SHOULD INCLUDE THE ROLE OF EPIGENETICS IN DETERMINING LONG-TERM AND LATE-ONSET HEALTH EFFECTS FOLLOWING CD EXPOSURE. 2012 14 1518 26 DNA METHYLATION AS AN EPIGENETIC MECHANISM IN THE DEVELOPMENT OF MULTIPLE SCLEROSIS. THE EPIGENETIC MECHANISMS OF GENE EXPRESSION REGULATION ARE A GROUP OF THE KEY CELLULAR AND MOLECULAR PATHWAYS THAT LEAD TO INHERITED ALTERATIONS IN GENES' ACTIVITY WITHOUT CHANGING THEIR CODING SEQUENCE. DNA METHYLATION AT THE C5 POSITION OF CYTOSINE IN CPG DINUCLEOTIDES IS AMONGST THE CENTRAL EPIGENETIC MECHANISMS. CURRENTLY, THE NUMBER OF STUDIES THAT ARE DEVOTED TO THE IDENTIFICATION OF METHYLATION PATTERNS SPECIFIC TO MULTIPLE SCLEROSIS (MS), A SEVERE CHRONIC AUTOIMMUNE DISEASE OF THE CENTRAL NERVOUS SYSTEM, IS ON A RAPID RISE. HOWEVER, THE ISSUE OF THE CONTRIBUTION OF DNA METHYLATION TO THE DEVELOPMENT OF THE DIFFERENT CLINICAL PHENOTYPES OF THIS HIGHLY HETEROGENEOUS DISEASE HAS ONLY BEGUN TO ATTRACT THE ATTENTION OF RESEARCHERS. THIS REVIEW SUMMARIZES THE DATA ON THE MOLECULAR MECHANISMS UNDERLYING DNA METHYLATION AND THE MS RISK FACTORS THAT CAN AFFECT THE DNA METHYLATION PROFILE AND, THEREBY, MODULATE THE EXPRESSION OF THE GENES INVOLVED IN THE DISEASE'S PATHOGENESIS. THE FOCUS OF OUR ATTENTION IS CENTERED ON THE ANALYSIS OF THE PUBLISHED DATA ON THE DIFFERENTIAL METHYLATION OF DNA FROM VARIOUS BIOLOGICAL SAMPLES OF MS PATIENTS OBTAINED USING BOTH THE CANDIDATE GENE APPROACH AND HIGH-THROUGHPUT METHODS. 2021 15 2360 25 EPIGENETIC REGULATION OF SKELETAL MUSCLE METABOLISM. NORMAL SKELETAL MUSCLE METABOLISM IS ESSENTIAL FOR WHOLE BODY METABOLIC HOMOEOSTASIS AND DISRUPTIONS IN MUSCLE METABOLISM ARE ASSOCIATED WITH A NUMBER OF CHRONIC DISEASES. TRANSCRIPTIONAL CONTROL OF METABOLIC ENZYME EXPRESSION IS A MAJOR REGULATORY MECHANISM FOR MUSCLE METABOLIC PROCESSES. SUBSTANTIAL EVIDENCE IS EMERGING THAT HIGHLIGHTS THE IMPORTANCE OF EPIGENETIC MECHANISMS IN THIS PROCESS. THIS REVIEW WILL EXAMINE THE IMPORTANCE OF EPIGENETICS IN THE REGULATION OF MUSCLE METABOLISM, WITH A PARTICULAR EMPHASIS ON DNA METHYLATION AND HISTONE ACETYLATION AS EPIGENETIC CONTROL POINTS. THE EMERGING CROSS-TALK BETWEEN METABOLISM AND EPIGENETICS IN THE CONTEXT OF HEALTH AND DISEASE WILL ALSO BE EXAMINED. THE CONCEPT OF INHERITANCE OF SKELETAL MUSCLE METABOLIC PHENOTYPES WILL BE DISCUSSED, IN ADDITION TO EMERGING EPIGENETIC THERAPIES THAT COULD BE USED TO ALTER MUSCLE METABOLISM IN CHRONIC DISEASE STATES. 2016 16 528 21 ASTHMA EPIGENETICS. ASTHMA IS THE MOST COMMON CHRONIC DISEASE OF CHILDHOOD, AND A GROWING BODY OF EVIDENCE INDICATES THAT EPIGENETIC VARIATIONS MAY MEDIATE THE EFFECTS OF ENVIRONMENTAL EXPOSURES ON THE DEVELOPMENT AND NATURAL HISTORY OF ASTHMA. EPIGENETICS IS THE STUDY OF MITOTICALLY OR MEIOTICALLY HERITABLE CHANGES IN GENE EXPRESSION THAT OCCUR WITHOUT DIRECTLY ALTERING THE DNA SEQUENCE. DNA METHYLATION, HISTONE MODIFICATIONS AND MICRORNAS ARE MAJOR EPIGENETIC VARIATIONS IN HUMANS THAT ARE CURRENTLY BEING INVESTIGATED FOR ASTHMA ETIOLOGY AND NATURAL HISTORY. DNA METHYLATION RESULTS FROM ADDITION OF A METHYL GROUP TO THE 5 POSITION OF A CYTOSINE RING AND OCCURS ALMOST EXCLUSIVELY ON A CYTOSINE IN A CPG DINUCLEOTIDE. HISTONE MODIFICATIONS INVOLVE POSTTRANSLATIONAL MODIFICATIONS SUCH AS ACETYLATION, METHYLATION, PHOSPHORYLATION AND UBIQUITINATION ON THE TAILS OF CORE HISTONES. MICRORNAS ARE SHORT ~22 NUCLEOTIDE LONG, NON-CODING, SINGLE-STRANDED RNAS THAT BINDS TO COMPLEMENTARY SEQUENCES IN THE TARGET MRNAS, USUALLY RESULTING IN GENE SILENCING. WHILE MANY STUDIES HAVE DOCUMENTED RELATIONSHIPS OF ENVIRONMENTAL EXPOSURES THAT HAVE BEEN IMPLICATED IN ASTHMA ETIOLOGY WITH EPIGENETIC ALTERATIONS, TO DATE, FEW STUDIES HAVE DIRECTLY LINKED EPIGENETIC VARIATIONS WITH ASTHMA DEVELOPMENT. THERE ARE SEVERAL METHODOLOGICAL CHALLENGES IN STUDYING THE EPIGENETICS OF ASTHMA. IN THIS CHAPTER, THE INFLUENCE OF EPIGENETIC VARIATIONS ON ASTHMA PATHOPHYSIOLOGY, METHODOLOGICAL CONCERNS IN CONDUCTING EPIGENETIC RESEARCH AND FUTURE DIRECTION OF ASTHMA EPIGENETICS RESEARCH ARE DISCUSSED. 2014 17 6199 29 THE IMPORTANCE OF EPIGENETICS IN THE DEVELOPMENT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE. IT IS GENERALLY ACCEPTED THAT GENETIC PREDISPOSITION PLAYS A ROLE IN COPD DEVELOPMENT IN SUSCEPTIBLE INDIVIDUALS. THEREFORE, MANY CANDIDATE GENES THAT COULD BE LINKED TO THE DEVELOPMENT OF DISEASE HAVE BEEN EXAMINED IN COPD. HOWEVER, INCONSISTENT RESULTS IN DIFFERENT STUDY POPULATIONS OFTEN LIMIT THIS APPROACH, SUGGESTING THAT NOT ONLY GENETICS, BUT ALSO OTHER FACTORS, MAY BE CONTRIBUTED TO THE SUSCEPTIBILITY TO COPD. EPIGENETIC MECHANISMS CAN AFFECT THE TRANSCRIPTIONAL ACTIVITY OF SPECIFIC GENES, AT DIFFERENT POINTS IN TIME, AND IN DIFFERENT ORGANS. MOREOVER, THESE MECHANISMS CAN HAVE AN EFFECT ON PEOPLE'S HEALTH. RECENTLY, THERE IS EMERGING EVIDENCE SUPPORTING A ROLE OF EPIGENETICS FOR THE REGULATION OF INFLAMMATORY GENES IN DISEASES SUCH AS ASTHMA AND COPD. MOREOVER, RECENT STUDIES SUGGEST THAT THE CURRENTLY USED TREATMENTS INCLUDING CORTICOSTEROIDS MAY WORK THROUGH EPIGENETIC MECHANISMS. EPIGENETIC REGULATION CAN BE REPROGRAMMED, POTENTIALLY AFFECTING THE RISK, AETIOLOGY AND TREATMENT OF VARIOUS DISEASE STATES. THE EPIGENETICALLY INFLUENCED PHENOTYPE COULD BE REVERSED WITH DEMETHYLATING OR DEACETYLATING AGENTS, CONSISTENT WITH EPIGENETIC PLASTICITY. THE POSTNATAL REVERSIBILITY OF THESE METHYLATION OR ACETYLATION EVENTS MAY THEREFORE PROVIDE GOOD OPPORTUNITIES FOR INTERVENTION. THE RECOGNITION OF THE ROLE OF GENETIC AND EPIGENETIC MECHANISMS IN THE DEVELOPMENT OF COPD MAY IDENTIFY NOVEL TARGETS THAT HATCH NEW THERAPIES FOR PATIENTS WITH COPD. 2011 18 5376 31 RECENT DEVELOPMENTS IN EPIGENETICS OF ACUTE AND CHRONIC KIDNEY DISEASES. THE GROWING EPIDEMIC OF OBESITY AND DIABETES, THE AGING POPULATION AS WELL AS PREVALENCE OF DRUG ABUSE HAS LED TO SIGNIFICANT INCREASES IN THE RATES OF THE CLOSELY ASSOCIATED ACUTE AND CHRONIC KIDNEY DISEASES, INCLUDING DIABETIC NEPHROPATHY. FURTHERMORE, EVIDENCE SHOWS THAT PARENTAL BEHAVIOR AND DIET CAN AFFECT THE PHENOTYPE OF SUBSEQUENT GENERATIONS VIA EPIGENETIC TRANSMISSION MECHANISMS. THESE DATA SUGGEST A STRONG INFLUENCE OF THE ENVIRONMENT ON DISEASE SUSCEPTIBILITY AND THAT, APART FROM GENETIC SUSCEPTIBILITY, EPIGENETIC MECHANISMS NEED TO BE EVALUATED TO GAIN CRITICAL NEW INFORMATION ABOUT KIDNEY DISEASES. EPIGENETICS IS THE STUDY OF PROCESSES THAT CONTROL GENE EXPRESSION AND PHENOTYPE WITHOUT ALTERATIONS IN THE UNDERLYING DNA SEQUENCE. EPIGENETIC MODIFICATIONS, INCLUDING CYTOSINE DNA METHYLATION AND COVALENT POST-TRANSLATIONAL MODIFICATIONS OF HISTONES IN CHROMATIN, ARE PART OF THE EPIGENOME, THE INTERFACE BETWEEN THE STABLE GENOME AND THE VARIABLE ENVIRONMENT. THIS DYNAMIC EPIGENETIC LAYER RESPONDS TO EXTERNAL ENVIRONMENTAL CUES TO INFLUENCE THE EXPRESSION OF GENES ASSOCIATED WITH DISEASE STATES. THE FIELD OF EPIGENETICS HAS SEEN REMARKABLE GROWTH IN THE PAST FEW YEARS WITH SIGNIFICANT ADVANCES IN BASIC BIOLOGY, CONTRIBUTIONS TO HUMAN DISEASE, AS WELL AS EPIGENOMICS TECHNOLOGIES. FURTHER UNDERSTANDING OF HOW THE RENAL CELL EPIGENOME IS ALTERED BY METABOLIC AND OTHER STIMULI CAN YIELD NOVEL NEW INSIGHTS INTO THE PATHOGENESIS OF KIDNEY DISEASES. IN THIS REVIEW, WE HAVE DISCUSSED THE CURRENT KNOWLEDGE ON THE ROLE OF EPIGENETIC MECHANISMS (PRIMARILY DNAME AND HISTONE MODIFICATIONS) IN ACUTE AND CHRONIC KIDNEY DISEASES, AND THEIR TRANSLATIONAL POTENTIAL TO IDENTIFY MUCH NEEDED NEW THERAPIES. 2015 19 860 31 CHROMATIN MODIFICATIONS DURING REPAIR OF ENVIRONMENTAL EXPOSURE-INDUCED DNA DAMAGE: A POTENTIAL MECHANISM FOR STABLE EPIGENETIC ALTERATIONS. EXPOSURES TO ENVIRONMENTAL TOXICANTS AND TOXINS CAUSE EPIGENETIC CHANGES THAT LIKELY PLAY A ROLE IN THE DEVELOPMENT OF DISEASES ASSOCIATED WITH EXPOSURE. THE MECHANISM BEHIND THESE EXPOSURE-INDUCED EPIGENETIC CHANGES IS CURRENTLY UNKNOWN. ONE COMMONALITY BETWEEN MOST ENVIRONMENTAL EXPOSURES IS THAT THEY CAUSE DNA DAMAGE EITHER DIRECTLY OR THROUGH CAUSING AN INCREASE IN REACTIVE OXYGEN SPECIES, WHICH CAN DAMAGE DNA. LIKE TRANSCRIPTION, DNA DAMAGE REPAIR MUST OCCUR IN THE CONTEXT OF CHROMATIN REQUIRING BOTH HISTONE MODIFICATIONS AND ATP-DEPENDENT CHROMATIN REMODELING. THESE CHROMATIN CHANGES AID IN DNA DAMAGE ACCESSIBILITY AND SIGNALING. SEVERAL PROTEINS AND COMPLEXES INVOLVED IN EPIGENETIC SILENCING DURING BOTH DEVELOPMENT AND CANCER HAVE BEEN FOUND TO BE LOCALIZED TO SITES OF DNA DAMAGE. THE CHROMATIN-BASED RESPONSE TO DNA DAMAGE IS CONSIDERED A TRANSIENT EVENT, WITH CHROMATIN BEING RESTORED TO NORMAL AS DNA DAMAGE REPAIR IS COMPLETED. HOWEVER, IN INDIVIDUALS CHRONICALLY EXPOSED TO ENVIRONMENTAL TOXICANTS OR WITH CHRONIC INFLAMMATORY DISEASE, REPEATED DNA DAMAGE-INDUCED CHROMATIN REARRANGEMENT MAY ULTIMATELY LEAD TO PERMANENT EPIGENETIC ALTERATIONS. UNDERSTANDING THE MECHANISM BEHIND EXPOSURE-INDUCED EPIGENETIC CHANGES WILL ALLOW US TO DEVELOP STRATEGIES TO PREVENT OR REVERSE THESE CHANGES. THIS REVIEW FOCUSES ON EPIGENETIC CHANGES AND DNA DAMAGE INDUCED BY ENVIRONMENTAL EXPOSURES, THE CHROMATIN CHANGES THAT OCCUR AROUND SITES OF DNA DAMAGE, AND HOW THESE TRANSIENT CHROMATIN CHANGES MAY LEAD TO HERITABLE EPIGENETIC ALTERATIONS AT SITES OF CHRONIC EXPOSURE. 2014 20 4216 26 METHYL DONOR MICRONUTRIENTS: A POTENTIAL DIETARY EPIGENETIC TARGET IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS. SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) IS A CHRONIC AUTOIMMUNE DISEASE CHARACTERIZED BY AN ABERRANT IMMUNE RESPONSE AND PERSISTENT INFLAMMATION. ITS PATHOGENESIS REMAINS UNKNOWN; HOWEVER, A COMPLEX INTERACTION BETWEEN ENVIRONMENTAL, GENETIC, AND EPIGENETIC FACTORS HAS BEEN SUGGESTED TO CAUSE DISEASE ONSET. SEVERAL STUDIES HAVE DEMONSTRATED THAT EPIGENETIC ALTERATIONS, SUCH AS DNA HYPOMETHYLATION, MIRNA OVEREXPRESSION, AND ALTERED HISTONE ACETYLATION, MAY CONTRIBUTE TO SLE ONSET AND THE DISEASE'S CLINICAL MANIFESTATIONS. EPIGENETIC CHANGES, ESPECIALLY METHYLATION PATTERNS, ARE MODIFIABLE AND SUSCEPTIBLE TO ENVIRONMENTAL FACTORS SUCH AS DIET. IT IS WELL KNOWN THAT METHYL DONOR NUTRIENTS, SUCH AS FOLATE, METHIONINE, CHOLINE, AND SOME B VITAMINS, PLAY A RELEVANT ROLE IN DNA METHYLATION BY PARTICIPATING AS METHYL DONORS OR COENZYMES IN ONE-CARBON METABOLISM. BASED ON THIS KNOWLEDGE, THIS CRITICAL LITERATURE REVIEW AIMED TO INTEGRATE THE EVIDENCE IN ANIMAL MODELS AND HUMANS REGARDING THE ROLE OF NUTRIENTS IN EPIGENETIC HOMEOSTASIS AND THEIR IMPACT ON IMMUNE SYSTEM REGULATION TO SUGGEST A POTENTIAL EPIGENETIC DIET THAT COULD SERVE AS ADJUVANT THERAPY IN SLE. 2023