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Abstract
Objective: This study aims to review existing literature on the impact of epigenetic modifications, including DNA methylation, histone modifications, and non-coding RNA, on gene expression and their implications for human health and disease mechanisms. Methods: A literature review was conducted between January 2023 and October 2024, analyzing nine selected studies that explored the relationship between epigenetic mechanisms and gene expression in patients with various conditions, such as heart disease and cancer. Key methodologies discussed include RNA sequencing (RNA-Seq) for quantifying gene expression, chromatin immunoprecipitation sequencing (ChIP-Seq) for protein-DNA interaction analysis, and DNA microarray analysis for genome-wide gene expression profiling. Results: The findings highlight that DNA methylation suppresses gene expression by chemically modifying DNA, histone modifications alter chromatin structure to regulate gene accessibility, and non-coding RNAs influence transcription and translation processes. The interplay among these mechanisms was shown to regulate gene expression without requiring genetic mutations, resulting in diverse biological outcomes. The review also discusses the role of daily nutrition, potential complications, and therapeutic strategies targeting epigenetic modifications. Novelty: This study underscores the critical role of epigenetic changes in modulating gene expression and provides insights into their potential for advancing the understanding of disease mechanisms and developing novel approaches for diagnosis, treatment, and prevention.
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References
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References
A. Bird, "Perceptions of Epigenetics," Nature, vol. 447, no. 7143, pp. 396–398, 2007.
R. A. Irizarry et al., "The Human Colon Cancer Methylome Shows Similar Hypo- and Hypermethylation at Conserved Tissue-Specific CpG Island Shores," Nature Genetics, vol. 41, no. 2, pp. 178–186, 2009.
R. A. Irizarry, H. Wu, and A. P. Feinberg, "A Species-Generalized Probabilistic Model-Based Definition of CpG Islands," Mammalian Genome, vol. 20, no. 9–10, pp. 674–680, 2009.
N. Sengupta and E. Seto, "Regulation of Histone Deacetylase Activities," Journal of Cellular Biochemistry, vol. 93, no. 1, pp. 57–67, 2004.
J. T. Bell et al., "DNA Methylation Patterns Associate with Genetic and Gene Expression Variation in HapMap Cell Lines," Genome Biology, vol. 12, no. 1, Art. no. R10, 2011.
J. R. Gibbs et al., "Abundant Quantitative Trait Loci Exist for DNA Methylation and Gene Expression in the Human Brain," PLoS Genetics, vol. 6, no. 5, Art. no. e1000952, 2010.
D. Zhang et al., "Genetic Control of Individual Differences in Gene-Specific Methylation in Human Brain," American Journal of Human Genetics, vol. 86, no. 3, pp. 411–419, 2010.
S. A. Monks et al., "Genetic Inheritance of Gene Expression in Human Cell Lines," American Journal of Human Genetics, vol. 75, no. 6, pp. 1094–1105, 2004.
M. P. Boks et al., "The Relationship of DNA Methylation with Age, Gender, and Genotype in Twins and Healthy Controls," PLoS One, vol. 4, no. 8, Art. no. e6767, 2009.
W. Cookson et al., "Mapping Complex Disease Traits with Global Gene Expression," Nature Reviews Genetics, vol. 10, no. 3, pp. 184–194, 2009.
B. E. Stranger and E. T. Dermitzakis, "The Genetics of Regulatory Variation in the Human Genome," Human Genomics, vol. 2, no. 2, pp. 126–131, 2005.
B. E. Stranger et al., "Relative Impact of Nucleotide and Copy Number Variation on Gene Expression Phenotypes," Science, vol. 315, no. 5813, pp. 848–853, 2007.
A. C. Nica et al., "The Architecture of Gene Regulatory Variation Across Multiple Human Tissues: The MuTHER Study," PLoS Genetics, vol. 7, no. 2, Art. no. e1002003, 2011.
B. E. Stranger et al., "Population Genomics of Human Gene Expression," Nature Genetics, vol. 39, no. 10, pp. 1217–1224, 2007.
S. Ghosh et al., "Tissue-Specific DNA Methylation of CpG Islands in Normal Human Adult Somatic Tissues Distinguishes Neural from Non-Neural Tissues," Epigenetics, vol. 5, no. 6, pp. 527–538, 2010.
P. Liang et al., "Genome-Wide Survey Reveals Dynamic Widespread Tissue-Specific Changes in DNA Methylation During Development," BMC Genomics, vol. 12, no. 1, Art. no. 231, 2011.
G. J. Huang et al., "High-Resolution Mapping of Expression QTLs in Heterogeneous Stock Mice in Multiple Tissues," Genome Research, vol. 19, no. 6, pp. 1133–1140, 2009.
E. Petretto et al., "Heritability and Tissue Specificity of Expression Quantitative Trait Loci," PLoS Genetics, vol. 2, no. 10, Art. no. e172, 2006.
J. E. Aten et al., "Using Genetic Markers to Orient the Edges in Quantitative Trait Networks: The NEO Software," BMC Systems Biology, vol. 2, Art. no. 34, 2008.
Y. Chen et al., "Variations in DNA Elucidate Molecular Networks That Cause Disease," Nature, vol. 452, no. 7186, pp. 429–435, 2008.
M. Inouye et al., "An Immune Response Network Associated with Blood Lipid Levels," PLoS Genetics, vol. 6, no. 9, Art. no. e1001113, 2010.
C. L. Plaisier et al., "A Systems Genetics Approach Implicates USF1, FADS3, and Other Causal Candidate Genes for Familial Combined Hyperlipidemia," PLoS Genetics, vol. 5, no. 9, Art. no. e1000642, 2009.
A. P. Presson et al., "Integrated Weighted Gene Co-Expression Network Analysis with an Application to Chronic Fatigue Syndrome," BMC Systems Biology, vol. 2, Art. no. 95, 2008.
S. Purcell et al., "PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses," American Journal of Human Genetics, vol. 81, no. 3, pp. 559–575, 2007.
A. D. Johnson et al., "SNAP: A Web-Based Tool for Identification and Annotation of Proxy SNPs Using HapMap," Bioinformatics, vol. 24, no. 24, pp. 2938–2939, 2008.
P. Langfelder and S. Horvath, "WGCNA: An R Package for Weighted Correlation Network Analysis," BMC Bioinformatics, vol. 9, Art. no. 559, 2008.
B. Zhang and S. Horvath, "A General Framework for Weighted Gene Co-Expression Network Analysis," Statistical Applications in Genetics and Molecular Biology, vol. 4, Art. no. 17, 2005.
P. Langfelder et al., "Is My Network Module Preserved and Reproducible?" PLoS Computational Biology, vol. 7, no. 1, Art. no. e1001057, 2011.
J. L. Peirce et al., "How Replicable Are mRNA Expression QTL?" Mammalian Genome, vol. 17, no. 6, pp. 643–656, 2006.
A. van Nas et al., "Expression Quantitative Trait Loci: Replication, Tissue-, and Sex-Specificity in Mice," Genetics, vol. 185, no. 3, pp. 1059–1068, 2010.
A. K. Maunakea et al., "Conserved Role of Intragenic DNA Methylation in Regulating Alternative Promoters," Nature, vol. 466, no. 7303, pp. 253–257, 2010.
S. Horvath, "Structural Equation Models and Directed Networks," in Weighted Network Analysis: Applications in Genomics and Systems Biology, New York: Springer, 2011, pp. 279–320.
R. C. Fry et al., "Genomic Predictors of Interindividual Differences in Response to DNA Damaging Agents," Genes & Development, vol. 22, no. 19, pp. 2621–2626, 2008.
S. G. Jin, S. Kadam, and G. P. Pfeifer, "Examination of the Specificity of DNA Methylation Profiling Techniques Towards 5-Methylcytosine and 5-Hydroxymethylcytosine," Nucleic Acids Research, vol. 38, no. 11, Art. no. e125, 2010.