Monday, October 19, 2009
What's the Connection between Hpa II and CpG Islands?
Epigenetics is all the rage today but the idea that gene expression could be regulated by modifying DNA and/or chromatin has been around for three decades.
Methylation is one of the ways that DNA can be modified and methylation at specific sites can be heritable. This observation grew out of studies on restriction/modification systems where DNA is protected from the action of restriction endonucleases by methylating the bases.
I didn't realize that the study of restriction enzymes led to the discovery of methylated regions of eukaryotic DNA. Find out how by reading an interview with Adrian Bird in PLoS Genetics: On the Track of DNA Methylation: An Interview with Adrian Bird.
This is also a good example of chance and serendipity in science. You can't plan for this stuff to happen—but that doesn't prevent politicians and administrators from trying.
Unfortunately, HpaII's isoschizomer MspI which also cuts methylated CpG dinucleotides in CCGG is not mentioned in that interview. It should be noted that methylated CpGs outside of CCGG are not identified by either of the two enzymes. Besides some other pairs of isoschizomers the comparison of HpaII digests which doesn't cut methylated sites with fully MspI digested DNA remained the only method to identify methylated DNA segments in eukaryotes for quite some time. To my best knowledge this is the first article describing this fact: Waalwijk C and Flavell RA (1978)MspI, an isoschizomer of hpaII which cleaves both unmethylated and methylated hpaII sites. Nucleic Acids Res 5(9):3231-6. (misspelling as hpaII in the original). Today Sodium bisulfite sequencing allows the identification of every single CpG dinucleotide.
ReplyDelete"Methylation is one of the ways that DNA can be modified and methylation at specific sites can be heritable"
ReplyDeleteVeeeery good larry. You're making baby steps of progress here!
Maybe next you'll even admit the fact that the environment can induce methylation.
"You can plan"? I believe you meant the negative, or "You can't plan".
ReplyDeleteThanks Dunbar.
ReplyDelete