Sandbox Reserved 592: Difference between revisions
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== Background == | == Background == | ||
[[Image:picture 1.jpg | 300 px | thumb |middle|Figure 1 showing the methylation of the histone protein and the subsequent formation of heterochromatin]] | |||
[[Image:picture 1.jpg | 300 px | thumb |Figure 1 showing the methylation of the histone protein and the subsequent formation of heterochromatin]] | |||
SUV39h1 is part of a class of methytransferase that deals with the methylation of histone proteins in nucleosomes. It is one of the very first histone methyltransferase to be discovered <ref>PMID:17320507</ref>. The methylation of histone proteins is an essential part of an area of genetics which deals with the modification of histone proteins called epigenomics. Epigenomics is the study of modifications of nucleosomes, which either inhibit or express gene transcription without changing the underlining DNA sequence. These changes are allowed because of the amino acid tails which extend out and away from the histone proteins, exposing itself to methylation. Methylation of histone protein is one of many ways that regulates gene expression. The regulation of gene expression is dependent on the state of the gene. A gene cannot be transcribed when the promoter of the gene is wrapped around the nucleosome, forming a heterochromatin state; thus, the gene is inhibited from being transcribed. Conversely, Methylation of the histone protein causes the winding around the nucleosomes, transforming a euchromatin state into a heterochromatin state. Of course, SUV39H1 alone does not methylate the histone proteins. SUV39H1 interacts with other proteins in order to efficiently methylate a histone protein (shown in Figure 1). Abnormal expression of genes, which is the result of down regulation or mutation of SUV39H1, results in a variety of diseases. | SUV39h1 is part of a class of methytransferase that deals with the methylation of histone proteins in nucleosomes. It is one of the very first histone methyltransferase to be discovered <ref>PMID:17320507</ref>. The methylation of histone proteins is an essential part of an area of genetics which deals with the modification of histone proteins called epigenomics. Epigenomics is the study of modifications of nucleosomes, which either inhibit or express gene transcription without changing the underlining DNA sequence. These changes are allowed because of the amino acid tails which extend out and away from the histone proteins, exposing itself to methylation. Methylation of histone protein is one of many ways that regulates gene expression. The regulation of gene expression is dependent on the state of the gene. A gene cannot be transcribed when the promoter of the gene is wrapped around the nucleosome, forming a heterochromatin state; thus, the gene is inhibited from being transcribed. Conversely, Methylation of the histone protein causes the winding around the nucleosomes, transforming a euchromatin state into a heterochromatin state. Of course, SUV39H1 alone does not methylate the histone proteins. SUV39H1 interacts with other proteins in order to efficiently methylate a histone protein (shown in Figure 1). Abnormal expression of genes, which is the result of down regulation or mutation of SUV39H1, results in a variety of diseases. | ||
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=== Chromodomain Structure === | === Chromodomain Structure === | ||
Crystal structure shows two main parts to the protein, but as a whole three independent molecules. There is a chromodomain and SET domain. The chromodomain starts at the N-terminus of the enzyme and continues toward the C-terminus, where the SET catalytic domain is located. The chromodomain length is around 44-106 amino acids long, which forms three anti- parallel beta sheets. The lengths for each of three beta sheets are 45-53, 58-64 and 73-76 amino acids long for beta 1, beta 2 and beta 3, respectively ( shown in figure 2). These three beta sheets form the chromodomain. | Crystal structure shows two main parts to the protein, but as a whole three independent molecules. There is a chromodomain and SET domain. The chromodomain starts at the N-terminus of the enzyme and continues toward the C-terminus, where the SET catalytic domain is located. The chromodomain length is around 44-106 amino acids long, which forms three anti- parallel beta sheets. The lengths for each of three beta sheets are 45-53, 58-64 and 73-76 amino acids long for beta 1, beta 2 and beta 3, respectively ( shown in figure 2). These three beta sheets form the chromodomain. | ||
[[Image:YFP.jpg| 400 px | thumb |left| Figure 2 shows the residue and tertiary and Quaternary structure SUV39H1]] | |||
[[Image:YFP.jpg| 400 px | thumb | Figure 2 shows the residue and tertiary and Quaternary structure SUV39H1]] | |||
=== SET Structure === | === SET Structure === | ||
<Structure load='3mts' size='400' frame='true' align='middle' caption='Insert caption here' scene='Insert optional scene name here' /> | <Structure load='3mts' size='400' frame='true' align='middle' caption='Insert caption here' scene='Insert optional scene name here' /> | ||
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== Clinical relevence == | == Clinical relevence == | ||
[[Image:picture 3.jpg | 300 px | thumb |Figure 3 showing the methylation of the histone protein and the subsequent formation of heterochromatin]] | [[Image:picture 3.jpg | 300 px | thumb |left|Figure 3 showing the methylation of the histone protein and the subsequent formation of heterochromatin]] | ||
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:11701123</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:11701123</ref>. | ||
