Arguing Over the Epigenome
31/03/10 11:47 Filed in: GenomeWeb Daily Scan
Submitted by S. Pelech - Kinexus on Tue, 04/06/2010 - 15:32.
Epigenomics is the study of the reversible covalent modification of DNA by methylation. This can lead to the silencing of genes in animals during development, and even across generations. Only about 3 DNA methyltransferases appear to account for CpG methylations in mammals. It still seems to be a mystery how the selectivity in gene methylation actually arises, even though 60 to 90% of mammalian genes are subject to this type of control. The lack of specificity associated with DNA methylation actually makes it rather unattractive for biomarker discovery and therapeutics development.
While the International Human Epigenome Consortium was formed to promote advancement in epigenomics research, the same certainly cannot be said for the major mode of reversible covalent modification of proteins. Over 500 different human protein kinases catalyze the reversible phosphorylation of almost all of the protein encoded by the human genome at probably more than 500,000 sites. It is regrettable that only a few laboratories in the world have the resources to conduct wide scale protein phosphorylation analysis to improve our understanding of its profound impact on cellular function and disease. There already exists a wealth of support for specific phospho-sites in proteins as biomarkers and protein kinases as useful drug targets. The Human Proteome Organization (HUPO) has no initiatives devoted specifically to mapping phosphorylation and other post-translational modifications of proteins. Kinexus Bioinformatics Corporation has undertaken to map the human phosphoproteome and provide such information as a free resource through www.phosphonet.ca.
I do agree with the others mentioned above that differences in species can be largely accounted for by the subtle differences in the oligonucleotide sequences of their genomes rather than epigenomics. A wonderful example of this is the well documented FoxP2 gene. Two point mutations in this gene in humans compared to other simians and mammals have contributed in a major way to our ability to speak and therefore even discuss such topics as DNA methylation and protein phosphorylation.
Link to the original blog post
Epigenomics is the study of the reversible covalent modification of DNA by methylation. This can lead to the silencing of genes in animals during development, and even across generations. Only about 3 DNA methyltransferases appear to account for CpG methylations in mammals. It still seems to be a mystery how the selectivity in gene methylation actually arises, even though 60 to 90% of mammalian genes are subject to this type of control. The lack of specificity associated with DNA methylation actually makes it rather unattractive for biomarker discovery and therapeutics development.
While the International Human Epigenome Consortium was formed to promote advancement in epigenomics research, the same certainly cannot be said for the major mode of reversible covalent modification of proteins. Over 500 different human protein kinases catalyze the reversible phosphorylation of almost all of the protein encoded by the human genome at probably more than 500,000 sites. It is regrettable that only a few laboratories in the world have the resources to conduct wide scale protein phosphorylation analysis to improve our understanding of its profound impact on cellular function and disease. There already exists a wealth of support for specific phospho-sites in proteins as biomarkers and protein kinases as useful drug targets. The Human Proteome Organization (HUPO) has no initiatives devoted specifically to mapping phosphorylation and other post-translational modifications of proteins. Kinexus Bioinformatics Corporation has undertaken to map the human phosphoproteome and provide such information as a free resource through www.phosphonet.ca.
I do agree with the others mentioned above that differences in species can be largely accounted for by the subtle differences in the oligonucleotide sequences of their genomes rather than epigenomics. A wonderful example of this is the well documented FoxP2 gene. Two point mutations in this gene in humans compared to other simians and mammals have contributed in a major way to our ability to speak and therefore even discuss such topics as DNA methylation and protein phosphorylation.
Link to the original blog post