Animal Molecular Breeding 2024, Vol.14, No.4, 262-270 http://animalscipublisher.com/index.php/amb 263 2 Epigenetic Mechanisms in Disease Resistance 2.1 DNA methylation DNA methylation is a crucial epigenetic modification that involves the addition of a methyl group to the DNA molecule, typically at cytosine bases in CpG dinucleotides (Zhou et al., 2020). This process can regulate gene expression by altering the accessibility of the DNA to transcriptional machinery, thereby playing a significant role in genomic stability and disease resistance. For instance, DNA methylation-related long non-coding RNAs (lncRNAs) have been shown to modulate gene expression by interacting with chromosomal modifications or remodeling factors, which can impact the progression of diseases such as lower-grade gliomas (LGGs). Additionally, DNA methylation is a reversible modification, making it a potential target for therapeutic interventions in various diseases (Izquierdo and Crujeiras, 2019). 2.2 Histone modifications Histone modifications, including acetylation, methylation, phosphorylation, and ubiquitination, are another layer of epigenetic regulation that influences chromatin structure and gene expression. These modifications can either promote or repress transcription depending on the specific type and location of the modification. Histone deacetylation and methylation inhibitors have been approved for clinical use in treating hematological malignancies, highlighting their therapeutic potential (Begolli et al., 2019). Furthermore, lncRNAs have been found to interact with histone-modifying enzymes, thereby influencing histone modifications and contributing to disease resistance mechanisms (Gray et al., 2022). 2.3 Non-coding RNAs (miRNA, lncRNA) Non-coding RNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), play a pivotal role in the epigenetic regulation of gene expression. miRNAs are short non-coding RNAs that can silence gene expression post-transcriptionally, while lncRNAs can interact with chromatin and other epigenetic machinery to regulate gene expression. For example, miRNAs have been shown to be epigenetically regulated by DNA methylation and histone modifications, and their dysregulation is associated with various diseases, including cancers (Pathania et al., 2021). Similarly, lncRNAs are involved in a wide range of biological processes and can modulate gene expression through interactions with epigenetic regulators, contributing to disease resistance (Raei et al., 2021). 2.4 Interaction between epigenetics and genomic regulation The interaction between epigenetic mechanisms and genomic regulation is complex and involves multiple layers of control. Epigenetic modifications such as DNA methylation, histone modifications, and non-coding RNAs work in concert to regulate gene expression and maintain genomic stability. Disruption in these interactions can lead to disease progression and resistance to therapies. For instance, the crosstalk between lncRNAs and miRNAs has been shown to play a critical role in drug resistance in gastrointestinal cancers, highlighting the importance of understanding these interactions for developing effective therapeutic strategies5. Additionally, the integration of epigenetic and genomic data is essential for identifying novel biomarkers and therapeutic targets for disease resistance (Maimaiti et al., 2022). In summary, the study of epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNAs, provides valuable insights into the regulation of gene expression and disease resistance. Understanding the intricate interactions between these mechanisms and genomic regulation is crucial for developing novel therapeutic approaches and improving clinical outcomes (Piletič and Kunej, 2016). 3 Current Research on Epigenetic Markers in Canine Health 3.1 Identified epigenetic markers for disease resistance Recent studies have identified several epigenetic markers that play a crucial role in disease resistance in dogs. For instance, the epigenetic regulation of the ABCB1 gene has been shown to be significant in determining the multidrug resistance (MDR) phenotype in canine lymphoid tumor cell lines (Tomiyasu et al., 2014). Specifically, differences in DNA methylation and histone H3 acetylation were observed between drug-sensitive and drug-resistant cell lines, indicating that these epigenetic modifications are associated with the MDR phenotype. Additionally, research on canine malignant lymphoma has highlighted the potential of histone deacetylases and
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