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Created page with "<span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:Calibri,sans-serif"><span lang="EN-US" style="font-size:12.0pt"><span style="font-family..."
<span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:Calibri,sans-serif"><span lang="EN-US" style="font-size:12.0pt"><span style="font-family:" times="" new="" roman",serif"="">Why are Epigenetic Modifications Critical for Understanding Disease Mechanisms?<br/> <br/> Khadisha S.<br/> Ulsan National Institute of Science and Technology, June 2024</span></span></span></span></span><br/> <br/> <br/> <br/> <br/> <br/> <span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:Calibri,sans-serif"><span lang="EN-US" style="font-size:12.0pt"><span style="font-family:" times="" new="" roman",serif"="">'''Abstract'''<br/> This essay delves into the critical role of epigenetic modifications in unraveling disease mechanisms. It elucidates how DNA methylation, histone modifications, and non-coding RNAs regulate gene expression and contribute to disease pathogenesis. Additionally, it highlights the influence of lifestyle and external factors on shaping the epigenetic landscape. By understanding these complex interactions, researchers can develop innovative therapeutic interventions and personalized medicine approaches. The essay underscores the transformative potential of epigenetic therapies in disease management and the importance of a holistic approach to healthcare.</span></span></span></span></span><br/> <br/> <br/> <br/> <span style="font-size:11pt"><span style="line-height:107%"><span style="font-family:Calibri,sans-serif">'''<span lang="EN-US" style="font-size:12.0pt"><span style="line-height:107%"><span style="font-family:" times="" new="" roman",serif"="">Introduction</span></span></span>'''<br/> <span lang="EN-US" style="font-size:12.0pt"><span style="line-height:107%"><span style="font-family:" times="" new="" roman",serif"="">Epigenetic modifications are crucial for understanding disease mechanisms because they provide insight into how environmental factors and lifestyle choices can influence gene expression and contribute to the development and progression of diseases.</span></span></span><span lang="ru-KZ" style="font-size:12.0pt"><span style="line-height:107%"><span style="font-family:" times="" new="" roman",serif"="">Epigenetics involves changes in gene activity without altering the DNA sequence. These changes can affect how genes are turned on or off and can be passed down to subsequent generations. The primary epigenetic mechanisms include DNA methylation, histone modification, and non-coding RNA-associated gene silencing.</span></span></span><span lang="EN-US" style="font-size:12.0pt"><span style="line-height:107%"><span style="font-family:" times="" new="" roman",serif"="">This essay explores how these mechanisms are pivotal in disease causations and their potential in therapeutic interventions.<br/> '''DNA methylation'''<br/> DNA methylation is a process by which methyl groups are added to cytosine residues within CpG dinucleotides, leading to gene silencing.</span></span></span><span lang="ru-KZ" style="font-size:12.0pt"><span style="line-height:107%"><span style="font-family:" times="" new="" roman",serif"="">DNA</span></span></span><span lang="ru-KZ" style="font-size:12.0pt"><span style="line-height:107%"><span style="font-family:" times="" new="" roman",serif"="">methylation is often associated with the suppression of gene expression.</span></span></span><span lang="EN-US" style="font-size:12.0pt"><span style="line-height:107%"><span style="font-family:" times="" new="" roman",serif"="">F</span></span></span><span lang="EN-US" style="font-size:12.0pt"><span style="line-height:107%"><span style="font-family:" times="" new="" roman",serif"="">or example, the hypermethylation of the CDKN2A gene, which encodes the p16INK4a tumor suppressor, is common in various cancers. Therapeutic agents like 5-azacytidine and decitabine, which inhibit DNA methyltransferases, can reverse these aberrant methylation patterns and restore normal gene expression.<br/> '''Histone modification'''</span></span></span><br/> <span lang="EN-US" style="font-size:12.0pt"><span style="line-height:107%"><span style="font-family:" times="" new="" roman",serif"=""><span style="color:black">Histone modification includes acetylation, methylation and phosphorylation, and ubiquitination, which influence chromatin structure and gene expression. A diverse range of epigenetic markers known as histone posttranslational modifications are implicated in both the steady maintenance of restrictive chromatin and dynamic cellular activities including transcription and DNA repair. Dysregulation of histone modifications is linked to numerous diseases, including cancer and neurological disorders. For instance, mutations in histone-modifying enzymes can lead to abnormal gene expression profiles. Histone deacetylase (HDAC) inhibitors, such as vorinostat and romidepsin, have shown effectiveness in treating cancers by restoring normal acetylation patterns and reactivating suppressed genes.<br/> '''Non-coding RNAs'''</span></span></span></span><br/> <span lang="EN-US" style="font-size:12.0pt"><span style="line-height:107%"><span style="font-family:" times="" new="" roman",serif"="">Non-coding RNAs do not encode proteins, however they affect RNA stability and translation, influencing cellular function and disease development. For-example, miRNAs typically bind to complementary sequences in the 3' untranslated region (UTR) of target messenger RNAs (mRNAs). This binding can result in either degradation of the mRNA or inhibition of its translation into protein, a large number of miRNAs act as tumor suppressors or oncogenes. For instance, miR-21 is known to be overexpressed in various cancers and promotes tumor growth by targeting multiple tumor suppressor genes. lncRNAs can interact with transcription factors or chromatin-modifying complexes to enhance or repress the transcription of specific genes. By regulating the transcription of genes involved in cell proliferation, apoptosis, and metastasis, lncRNAs can promote or inhibit cancer.<br/> '''Effect of lifestyle and external''' '''factors'''<br/> Also we have to mention how lifestyle and external conditions like diet, physical activity, stress, exposure to toxins, and even social interactions can alter the epigenetic modifications.</span></span></span><span lang="ru-KZ" style="font-size:12.0pt"><span style="line-height:107%"><span style="font-family:" times="" new="" roman",serif"="">For instance, dietary components such as folate, vitamins B12 and B6, and methionine are vital for DNA methylation processes. A diet deficient in these nutrients can lead to hypomethylation and increased disease risk. Physical activity has been shown to induce beneficial epigenetic changes that promote health, whereas chronic stress can lead to harmful epigenetic modifications that increase the risk of mental health disorders and other diseases. Exposure to environmental toxins, such as tobacco smoke and air pollutants, can also induce aberrant DNA methylation and histone modifications, leading to diseases like cancer and cardiovascular disorders.</span></span></span><br/> <br/> <span lang="EN-US" style="font-size:12.0pt"><span style="line-height:107%"><span style="font-family:" times="" new="" roman",serif"="">Epigenetic signatures are valuable biomarkers for disease diagnosis, prognosis, and treatment response. Personalized epigenetic therapies can tailor treatments based on an individual's unique epigenetic profile, representing a shift towards precision medicine. This approach aims to maximize treatment efficacy and minimize adverse effects by targeting specific epigenetic changes unique to each patient's disease.</span></span></span><br/> <span lang="EN-US" style="font-size:12.0pt"><span style="line-height:107%"><span style="font-family:" times="" new="" roman",serif"="">Drugs targeting epigenetic modifications, such as DNA methylation inhibitors (e.g., 5-azacytidine) and histone deacetylase inhibitors (e.g., vorinostat), have shown efficacy in treating certain cancers by reversing abnormal epigenetic marks and restoring normal gene expression.</span></span></span></span></span></span><br/> <br/> <span style="font-size:12pt"><span style="line-height:115%"><span style="font-family:" times="" new="" roman",serif"="">'''Conclusion'''<br/> Epigenetic modifications are crucial for understanding disease mechanisms because they illustrate how genes and environmental factors interact to cause diseases. By discussing these regulatory networks, scientists can develop innovative therapeutic interventions and personalized medicine approaches. Lifestyle and environmental factors play a significant role in shaping these epigenetic changes, further highlighting the importance of a holistic approach to disease prevention and treatment. As research progresses, the potential for epigenetic therapies to transform disease management and improve patient outcomes is immense.</span></span></span><br/> <br/> '''Reference'''<br/> <span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:Calibri,sans-serif"><span lang="EN-US" style="font-size:12.0pt"><span style="font-family:" times="" new="" roman",serif"="">1. Esteller, M. Epigenetics in cancer. </span></span></span></span></span><br/> <span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:Calibri,sans-serif"><span lang="EN-US" style="font-size:12.0pt"><span style="font-family:" times="" new="" roman",serif"="">2. Jones, P. A., & Baylin, S. B. The fundamental role of epigenetic events in cancer. </span></span></span></span></span><br/> <span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:Calibri,sans-serif"><span lang="EN-US" style="font-size:12.0pt"><span style="font-family:" times="" new="" roman",serif"="">3. Kouzarides, T.Chromatin modifications and their function. </span></span></span></span></span><br/> <br/>
