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<p><span style="font-size:14px">Epigenomcis is the study of the complete set of <strong>epigenetic modifications</strong> on the genetic material of a cell, known as the epigenome.</span></p>
<p><span style="font-size:14px">{ <strong>Epigenetic modifications</strong> = genomic modifications that alter gene expression that cannot be attributed to modification </span></p>
<p><span style="font-size:14px"> of the primary DNA sequence and that are heritalbe mitotically and meiotically are classified }</span></p>
<p><u><span style="font-size:14px">## Major two types of epigenemic modifications ##</span></u></p>
<p><span style="font-size:14px">1) <strong>DNA methylation</strong></span></p>
<p><span style="font-size:14px">DNA methylation is the process of by which a methyl group is added to DNA by enzymes <strong>DNA methyltransferases (DNMTs)</strong> which are responsible for catalyzing this reaction. In <u>eukaryotes</u>, methylation is most commonly found on the <u>carbon 5 position of cytosine residues (5mc)</u> adjacent to guanine. DNA methylation patterns vary greatly between species and even with the same organisms. </span></p>
<p><span style="font-size:14px">2) <strong>Histone modification</strong></span></p>
<p>In eukaryotes, genomic DNA is coiled into protein-DNA complexes called chromatin. Histones, which are the most prevalent type of protein found in chromatin, function to condense the DNA; the net positive charge on histones facilitates their bonding with DNA, which is negatively charged. The basic and repeating units of chromatin, nucleosomes, consist of an octamer of histone proteins. Many different types of histone modification are known, including acetylation, methylation, phosphorylation, ubiquitination etc. The DNA region where histone modification occurs can elicit different effects. Histone modifications regulate gene expression by two mechanisms : by disruption of the contact between nucleosomes and by recruiting chromatin remodeling ATPases.</p>
<p><u><span style="font-size:14px">## Epigenomic methods ##</span></u></p>
<p><span style="font-size:14px">1) <strong>Histone modification assay</strong></span></p>
<p>The cellular processes of transcription, DNA replication and DNA repair involve the interaction between genomic DNA and nuclear proteins. It had been known that certain regions within chromatin were extremely susceptible to DNase I digestion, which cleaves DNA in a low sequence specificity manner. Such hypersensitive sites were thought to be transcriptionally active regions, as evidenced by their association with RNA polymerase and topoisomerase I and II. It is now known that sensitivity to DNAse I regions correspond to regions of chromatin with loose DNA-histone association. Hypersensitive sites most often represent promoters regions, which require for DNA to be accessible for DNA binding transcriptional machinery to function.</p>
<p>⑥ Analysis of the relative signal intensity allows the sites of histone modification to be determined. </p>
<p>2) <strong>DNA methylation arrays</strong></p>
<p>Techniques for characterizing primary DNA sequences could not be directly applied to methylation assays. For example, when DNA was amplified in PCR or bacterial cloning techniques, the methylation pattern was not copied and thus the information lost. The DNA hybridization technique used in DNA assays, in which radioactive probes were used to map and identify DNA sequences, could not be used to distinguish between methylated and non-methylated DNA.</p>
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