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| − | <p> </p> | + | <p>[[genome]]</p> |
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| − | <p style="text-align: center;"><span style="font-size:24px">The DNA is not your destiny.- Epigenomics </span></p> | + | <p>[[sequencing]]</p> |
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| − | <p style="text-align: right;">Sangin Kim </p> | + | <p>[[alignment]]</p> |
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| − | <p> </p> | + | <p>[[genomics]]</p> |
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| − | <p><strong>Epigenomics</strong> is the study of the complete set of epigenetic modifications on the genetic material of a cell, known as the epigenome. The field is analogous to genomics and proteomics, which are the study of the genome and proteome of a cell (Russell 2010 p. 217 & 230). Epigenetic modifications are reversible modifications on a cell’s DNA or histones that affect gene expression without altering the DNA sequence . Epigenomic maintenance is a continuous process and plays an important role in stability of eukaryotic genomes by taking part in crucial biological mechanisms like DNA repair.Two of the most characterized epigenetic modifications are DNA methylation and histone modification. Epigenetic modifications play an important role in gene expression and regulation, and are involved in numerous cellular processes such as in differentiation / development and tumorigenesis. The study of epigenetics on a global level has been made possible only recently through the adaptation of genomic high-throughput assays. </p> | + | <p>[[omics]]</p> |
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| − | <p> </p> | + | <p>[[transcriptomics]]</p> |
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| − | <p>Genomic modifications that alter gene expression that cannot be attributed to modification of the primary DNA sequence and that are heritable <a href="https://en.wikipedia.org/wiki/Mitosis" title="Mitosis">mitotically</a> and <a href="https://en.wikipedia.org/wiki/Meiosis" title="Meiosis">meiotically</a> are classified as epigenetic modifications. DNA methylation and histone modification are among the best characterized epigenetic processe</p> | + | <p>[[epigenomics]]</p> |
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| − | <p> </p> | + | <p>[[microbiomics]]</p> |
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| − | <h3>DNA methylation[<a href="https://en.wikipedia.org/w/index.php?title=Epigenomics&action=edit&section=3" title="Edit section: DNA methylation">edit</a>]</h3> | + | <p>[[phenomics]]</p> |
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| − | <p>The first epigenetic modification to be characterized in depth was DNA methylation. As its name implies, DNA methylation is the process by which a <a href="https://en.wikipedia.org/wiki/Methyl_group" title="Methyl group">methyl group</a> is added to DNA. The enzymes responsible for catalyzing this reaction are the <a href="https://en.wikipedia.org/wiki/DNA_methyltransferase" title="DNA methyltransferase">DNA methyltransferases (DNMTs)</a>. While DNA methylation is stable and heritable, it can be reversed by an antagonistic group of enzymes known as DNA de-methylases. In eukaryotes, methylation is most commonly found on the carbon 5 position of <a href="https://en.wikipedia.org/wiki/Cytosine" title="Cytosine">cytosine residues</a> (5mC) adjacent to <a href="https://en.wikipedia.org/wiki/Guanine" title="Guanine">guanine</a>, termed <a href="https://en.wikipedia.org/wiki/CpG_site" title="CpG site">CpG dinucleotides</a> (Russell 2010 p 531-32; Laird 2010). DNA methylation patterns vary greatly between species and even within the same organism. The usage of methylation among animals is quite different; with <a href="https://en.wikipedia.org/wiki/Vertebrate" title="Vertebrate">vertebrates</a> exhibiting the highest levels of 5mC and <a href="https://en.wikipedia.org/wiki/Invertebrate" title="Invertebrate">invertebrates</a> more moderate levels of 5mC. Some organisms like <em><a href="https://en.wikipedia.org/wiki/Caenorhabditis_elegans" title="Caenorhabditis elegans">Caenorhabditis elegans</a></em> have not been demonstrated to have 5mC nor a conventional DNA methyltransferase; this would suggest that other mechanisms other than DNA methylation are also involved (Bird 2002).</p> | + | <p>[[geromics]]</p> |
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| − | <p>Within an organism, DNA methylation levels can also vary throughout development and by region. For example, in mouse primordial <a href="https://en.wikipedia.org/wiki/Germ_cell" title="Germ cell">germ cells</a>, a genome wide de-methylation even occurs; by implantation stage, methylation levels return to their prior somatic levels (Bird 2002). When DNA methylation occurs at <a href="https://en.wikipedia.org/wiki/Promoter_(biology)" title="Promoter (biology)">promoter regions</a>, the sites of transcription initiation, it has the effect of repressing gene expression. This is in contrast to unmethylated promoter regions which are associated with actively expressed genes (Laird 2010).</p>
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| − | <p>The mechanism by which DNA methylation represses gene expression is a multi-step process. The distinction between methylated and unmethylated cytosine residues is carried out by specific DNA-binding proteins. Binding of these proteins recruit <a href="https://en.wikipedia.org/wiki/Histone_deacetylase" title="Histone deacetylase">histone deacetylases (HDACs)</a> enzyme which initiate <a href="https://en.wikipedia.org/wiki/Epigenetics#DNA_methylation_and_chromatin_remodeling" title="Epigenetics">chromatin remodeling</a> such that the DNA becoming less accessible to transcriptional machinery, such as <a href="https://en.wikipedia.org/wiki/RNA_polymerase" title="RNA polymerase">RNA polymerase</a>, effectively repressing gene expression (Russell 2010 p. 532-533).</p>
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| − | <p> </p>
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| − | <h3>Histone Modification[<a href="https://en.wikipedia.org/w/index.php?title=Epigenomics&action=edit&section=4" title="Edit section: Histone Modification">edit</a>]</h3>
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| − | <p>In <a href="https://en.wikipedia.org/wiki/Eukaryote" title="Eukaryote">eukaryotes</a>, genomic DNA is coiled into protein-DNA complexes called <a href="https://en.wikipedia.org/wiki/Chromatin" title="Chromatin">chromatin</a>. <a href="https://en.wikipedia.org/wiki/Histone" title="Histone">Histones</a>, 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, <a href="https://en.wikipedia.org/wiki/Nucleosome" title="Nucleosome">nucleosomes</a>, consist of an <a href="https://en.wikipedia.org/wiki/Histone_octamer" title="Histone octamer">octamer of histone proteins</a> (H2A, H2B, H3 and H4) and a 146 bp length of DNA wrapped around it. Nucleosomes and the DNA connecting form a 10 nm diameter chromatin fiber, which can be further condensed (Barski et al. 2007; Kouzarides 2007).</p>
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| − | <p>Chromatin packaging of DNA varies depending on the cell cycle stage and by local DNA region (Russell 2010 p. 24-27). The degree to which chromatin is condensed is associated with a certain transcriptional state. Unpackaged or loose chromatin is more transcriptionally active than tightly packaged chromatin because it is more accessible to transcriptional machinery. By remodeling chromatin structure and changing the density of DNA packaging, gene expression can thus be modulated (Kouzarides 2007).</p>
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| − | <p>Chromatin remodeling occurs via <a href="https://en.wikipedia.org/wiki/Posttranslational_modification" title="Posttranslational modification">post-translational modifications</a> of the <a href="https://en.wikipedia.org/wiki/Nucleosome#Histone_tail_domains" title="Nucleosome">N-terminal tails of core histone proteins</a> (Russell 2010 p. 529-30). The collective set of histone modifications in a given cell is known as the <a href="https://en.wikipedia.org/wiki/Histone_code" title="Histone code">histone code</a>. Many different types of histone modification are known, including: <a href="https://en.wikipedia.org/wiki/Acetylation" title="Acetylation">acetylation</a>, <a href="https://en.wikipedia.org/wiki/Methylation" title="Methylation">methylation</a>, <a href="https://en.wikipedia.org/wiki/Phosphorylation" title="Phosphorylation">phosphorylation</a>, <a href="https://en.wikipedia.org/wiki/Ubiquitin" title="Ubiquitin">ubiquitination</a>, <a href="https://en.wikipedia.org/wiki/SUMO_protein" title="SUMO protein">SUMOylation</a>, <a href="https://en.wikipedia.org/wiki/ADP-ribosylation" title="ADP-ribosylation">ADP-ribosylation</a>, <a href="https://en.wikipedia.org/wiki/Citrullination" title="Citrullination">deamination</a> and <a href="https://en.wikipedia.org/wiki/Proline" title="Proline">proline isomerization</a>; acetylation, methylation, phosphorylation and ubiquitination have been implicated in gene activation whereas methylation, ubiquitination, SUMOylation, deamination and proline isomerization have been implicated in gene repression. Note that several modification types including methylation, phosphorylation and ubiquitination can be associated with different transcriptional states depending on the specific amino acid on the histone being modified. Furthermore, the DNA region where histone modification occurs can also elicit different effects; an example being methylation of the 3rd core histone at lysine residue 36 (H3K36). When H3K36 occurs in the coding sections of a gene, it is associated with gene activation but the opposite is found when it is within the promoter region (Kouzarides 2007).</p>
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| − | <p> </p>
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| − | <p> </p>
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| − | <h3>Histone modification assays[<a href="https://en.wikipedia.org/w/index.php?title=Epigenomics&action=edit&section=7" title="Edit section: Histone modification assays">edit</a>]</h3>
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| − | <p>The cellular processes of <a href="https://en.wikipedia.org/wiki/Transcription_(genetics)" title="Transcription (genetics)">transcription</a>, <a href="https://en.wikipedia.org/wiki/DNA_replication" title="DNA replication">DNA replication</a> and <a href="https://en.wikipedia.org/wiki/DNA_repair" title="DNA repair">DNA repair</a> involve the interaction between genomic DNA and nuclear proteins. It had been known that certain regions within chromatin were extremely susceptible to <a href="https://en.wikipedia.org/wiki/Deoxyribonuclease" title="Deoxyribonuclease">DNAse I</a> digestion, which cleaves DNA in a low sequence specificity manner. Such <a href="https://en.wikipedia.org/wiki/Hypersensitive_sites" title="Hypersensitive sites">hypersensitive sites</a> were thought to be transcriptionally active regions, as evidenced by their association with <a href="https://en.wikipedia.org/wiki/RNA_polymerase" title="RNA polymerase">RNA polymerase</a> and <a href="https://en.wikipedia.org/wiki/Topoisomerase" title="Topoisomerase">topoisomerases I and II</a> (Gross 1988).</p>
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| − | <p>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 (Russell 2010 p. 529).</p>
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| − | <p> </p>
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| − | <h3>DNA Methylation assays[<a href="https://en.wikipedia.org/w/index.php?title=Epigenomics&action=edit&section=9" title="Edit section: DNA Methylation assays">edit</a>]</h3>
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| − | <p>Techniques for characterizing primary DNA sequences could not be directly applied to methylation assays. For example, when DNA was amplified in <a href="https://en.wikipedia.org/wiki/Polymerase_chain_reaction" title="Polymerase chain reaction">PCR</a> or bacterial cloning techniques, the methylation pattern was not copied and thus the information lost. The <a href="https://en.wikipedia.org/wiki/Hybridization_probe" title="Hybridization probe">DNA hybridization technique</a> 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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| − | <p> </p>
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| − | <p>References</p>
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| − | <p>1. https://www.youtube.com/watch?v=zcJPXISDxkM</p>
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| − | <p>2. https://www.youtube.com/watch?v=D9CzvalZ2zY</p>
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| − | <p>3. https://www.youtube.com/watch?v=Udlz7CMLuLQ</p>
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| − | <p>4. https://www.youtube.com/watch?v=LWQfe__fNbs</p>
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| − | <p>5. https://en.wikipedia.org/wiki/Epigenomics</p>
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| − | <p> </p>
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