Sandbox Reserved 592: Difference between revisions
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The chromodomain structure of the enzyme (residues) is not involve in the catalytic function of the enzyme, but is very important to the binding to the molecule. Mutations which remove the chromodomain area of the enzyme result in the inhibition of the enzyme. The inhibition of the chromodomain prevents the methylating action of the enzyme's catalytic domain. Although the chromodomain is not directly involved in the methylation of the histone proteins, it plays an important role in the binding of the enzyme to histone proteins as well as other proteins. Fluorescence Polarization Assays have shown the chromodomain has a high affinity for the histone protein H3K9me1 and H3K9me2. SUV39H1 residues that did not contain the aromatic F34 cage did not bind to the histone protein. This shows the F34 is a conserved residue that is essential for the enzyme binding to the histone protein. Moreover, a mutation which results in the loss of the aromatic F34 cage group will inhibit the binding effect of the chromodomain enzymes. SUV39H1 does not methylate the histone protein alone; it is aided by other proteins. Studies have shown HP1 and H3 are essential proteins that combine with SUV39H1 in protein complex, which methylate the histone protein of a nucleosome <ref>PMID:12565857</ref>. | The chromodomain structure of the enzyme (residues) is not involve in the catalytic function of the enzyme, but is very important to the binding to the molecule. Mutations which remove the chromodomain area of the enzyme result in the inhibition of the enzyme. The inhibition of the chromodomain prevents the methylating action of the enzyme's catalytic domain. Although the chromodomain is not directly involved in the methylation of the histone proteins, it plays an important role in the binding of the enzyme to histone proteins as well as other proteins. Fluorescence Polarization Assays have shown the chromodomain has a high affinity for the histone protein H3K9me1 and H3K9me2. SUV39H1 residues that did not contain the aromatic F34 cage did not bind to the histone protein. This shows the F34 is a conserved residue that is essential for the enzyme binding to the histone protein. Moreover, a mutation which results in the loss of the aromatic F34 cage group will inhibit the binding effect of the chromodomain enzymes. SUV39H1 does not methylate the histone protein alone; it is aided by other proteins. Studies have shown HP1 and H3 are essential proteins that combine with SUV39H1 in protein complex, which methylate the histone protein of a nucleosome <ref>PMID:12565857</ref>. | ||
[[Image:picture ta.jpg| 300 px | thumb |right|Figure 4: The figure shows the essential molecule (SAM) needed for proper methylation of the histone protein.]] | |||
[[Image:picture 3.jpg | 300 px | thumb |left|Figure 5: The figure shows how tumor suppressor genes are silenced because of unregulated histone methyltransferases complex]] | |||
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== Clinical relevence == | == Clinical relevence == | ||
The physiological state of a cell depends on the physiological state of the genes which defines the function of the cell. Unregulated expression of genes in the cell leads to physiological and morphological change of the cell. Euchromatin and heterochromatin define the physiological state of a cell. Mutations and knockout studies of SUV39H1 in mice have shown to increase genomic instability. The instability arises from the inability of SUV39H1 to form heterochromatin. Since the enzyme could not methylate the nucleosomes and transform a euchromatin state into a heterochromatin state, certain genes were highly expressed, which lead to the instability of cells <ref>PMID:22583735</ref>. | The physiological state of a cell depends on the physiological state of the genes which defines the function of the cell. Unregulated expression of genes in the cell leads to physiological and morphological change of the cell. Euchromatin and heterochromatin define the physiological state of a cell. Mutations and knockout studies of SUV39H1 in mice have shown to increase genomic instability. The instability arises from the inability of SUV39H1 to form heterochromatin. Since the enzyme could not methylate the nucleosomes and transform a euchromatin state into a heterochromatin state, certain genes were highly expressed, which lead to the instability of cells <ref>PMID:22583735</ref>. | ||
Further knockout studies of SUV39H1 have shown that length of telomeres in mice and pigs have increased. The increase in the length of the telomeres also increases tumor genesis in pigs and mice. The previous studies, however, did not show a significant telomere growth in human cells. The results may indicate an epigenetic regulation that is more similar between pigs and mice than human <ref>PMID:23018532</ref>. | Further knockout studies of SUV39H1 have shown that length of telomeres in mice and pigs have increased. The increase in the length of the telomeres also increases tumor genesis in pigs and mice. The previous studies, however, did not show a significant telomere growth in human cells. The results may indicate an epigenetic regulation that is more similar between pigs and mice than human <ref>PMID:23018532</ref>. | ||
