mircoRNA cluster controlling DNA methylation and Telomere recombination
DNA methylation is one of the major type of epigenetic control. Here we discuss the role of the microRNA clusters in the controlling the DNA methylation indirectly controlling the telomere recombination.
This entire mechanism is Dicer dependent, a RNase III family nuclease that helps in formation of the microRNAs. Dicer helps in maintaining the level of DNA methyltransferases (Dnmts) in the cell which are responsible for the DNA CpG methylation, H3K9 and H4K20 methylation and also telomere methylation. The study shows that with the decrease in the expression or deletion of Dicer, DNA methylation defects are seen due to repression of Dnmts coding gene.
The research paper suggests a mechanism which makes use of Rbl2 protein to control the expression of the Dnmts genes, in a way controlling the Dnmts proteins. Rbl2 uses the enzyme histone deacetylases, causing deacetylation of Dnmts gene promoter (acetylation helps in activating of particular nucleosome) thereby repressing the formation of the Dnmts. The expression of these Rbl2 proteins is in-turn controlled (post transcriptional control) by Dicer dependent microRNA cluster (miR290).
Thus here we can see a cycle of events, where, if Dicer is present, we get expression of miR 290 cluster, which down-regulates the expression of Rbl2. Down regulation of Rbl2 leads to expression of Dnmts, thereby resulting in proper methylation pattern of the DNA. On contrary, Dicer abrogation, causes repression of miR 290 cluster, thus leading to formation of Rbl2 protein. This Rbl2 further on down-regulates the expression of Dnmts, thereby affecting the normal methylation pattern.
Here we can see that Dnmts repression causes defects in the DNA methylation. These defects are found especially in heterochromatic region of the chromosome (telomeric and subtelomeric regions). Methylation in case of the telomere is the major controlling factor of their length. Methylation of the telomere prevents the telomeric recombination and also telomeric elongation. Thus any defect in the methylation pattern of telomere can cause telomeric recombination/elongation which might become cancerous.
Finally we can say that the presence or absence of Dicer controls the entire mechanism of Telomeric recombination/ elongation, in a way controlling the abnormal cell growth.
Original Article, 'A mammalian microRNA cluster controls DNA methylation and telomere recombination via Rbl2-dependent regulation of DNA methyltransferses'
Authors: Roberta Benetti et. al.
Journal: Nature Structural and Molecular Biology, Volume 15 (3), March 2008. 268-279
Akshay Bhumkar.
This entire mechanism is Dicer dependent, a RNase III family nuclease that helps in formation of the microRNAs. Dicer helps in maintaining the level of DNA methyltransferases (Dnmts) in the cell which are responsible for the DNA CpG methylation, H3K9 and H4K20 methylation and also telomere methylation. The study shows that with the decrease in the expression or deletion of Dicer, DNA methylation defects are seen due to repression of Dnmts coding gene.
The research paper suggests a mechanism which makes use of Rbl2 protein to control the expression of the Dnmts genes, in a way controlling the Dnmts proteins. Rbl2 uses the enzyme histone deacetylases, causing deacetylation of Dnmts gene promoter (acetylation helps in activating of particular nucleosome) thereby repressing the formation of the Dnmts. The expression of these Rbl2 proteins is in-turn controlled (post transcriptional control) by Dicer dependent microRNA cluster (miR290).
Thus here we can see a cycle of events, where, if Dicer is present, we get expression of miR 290 cluster, which down-regulates the expression of Rbl2. Down regulation of Rbl2 leads to expression of Dnmts, thereby resulting in proper methylation pattern of the DNA. On contrary, Dicer abrogation, causes repression of miR 290 cluster, thus leading to formation of Rbl2 protein. This Rbl2 further on down-regulates the expression of Dnmts, thereby affecting the normal methylation pattern.
Here we can see that Dnmts repression causes defects in the DNA methylation. These defects are found especially in heterochromatic region of the chromosome (telomeric and subtelomeric regions). Methylation in case of the telomere is the major controlling factor of their length. Methylation of the telomere prevents the telomeric recombination and also telomeric elongation. Thus any defect in the methylation pattern of telomere can cause telomeric recombination/elongation which might become cancerous.
Finally we can say that the presence or absence of Dicer controls the entire mechanism of Telomeric recombination/ elongation, in a way controlling the abnormal cell growth.
Original Article, 'A mammalian microRNA cluster controls DNA methylation and telomere recombination via Rbl2-dependent regulation of DNA methyltransferses'
Authors: Roberta Benetti et. al.
Journal: Nature Structural and Molecular Biology, Volume 15 (3), March 2008. 268-279
Akshay Bhumkar.
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