A long time ago, I think on Pharyngula, Richard Dawkins said something that really pissed me off. Its been so long ago I cant find the right comment thread anymore, but Dawkins said something regarding epigenetics along the lines of “Um… isnt this just a fancy word for transcription regulation? Stuff weve been studying for years and years…” And I went all WARBLEGARBLE “OMG NO EPIGENETICS IS SO NEW AND DIFFERENT AND SO MUCH COOLER THAN TRANSCRIPTIONAL REGULATION OMFG RICHARD DAWKINS UR SUCH A N00B!!!”
I totally get it now. Ive slowly been getting it since that exchange, but I totally get it now. The final straw was this paper I just read on an ‘epigenetic modification’ of an HIV transcription regulator:
The Cellular lysine methyltransferase Set7/9-KMT7 binds HIV-1 TAR RNA, monomethylates the viral transactivator Tat, and enhances HIV transcription.
Histone and DNA modifications that alter chromatin structure–> gene expression. Some people also include siRNA.
Set7/9-KMT7 is a protein that methylates lysine 4 on histone 3. So, its an epigenetic modifier. Not magic. Not ‘bird song’ or ‘your cells have the power to change their genetics!’, its just a protein that sticks a methyl group (an epigenetic modification) on a histone.
Pagans et al report in this paper that Set7/9-KTM7 also modifies and interacts with an HIV-1 protein, Tat. Tat needs to be methylated by Set7/9-KTM7 (not any ol methyltransferase) at a very specific lysine (not any ol lysine) to do its job with the most efficiency.
Here is another way this is ‘epigenetics’– its not just the same protein that modifies histones and Tat, its that Tat itself has a role in transcription. Its a transcription factor, aiding in the transcription of HIV mRNA. But Tat is weird in that it does not bind to DNA, it binds to the first bit of HIV-1 mRNA, helping it along, so the entire transcripts are made.
If Tat is not present, all you would get are a bunch of aborted HIV-1 transcripts.
If Set7/9-KMT7 is not present to modify Tat (knock down protein expression with siRNA), you get some HIV-1 transcription, but its nothing compared to when Set7/9-KMT7 is there at normal (or over-expressed) levels.
Why is modifying a histone to alter gene transcription ‘EPIGENETICS!’ *jazzhands*, but the exact same modification on a different protein to alter gene transcription ‘only boring ol gene regulation’?
Is it inheritance?
These other examples dont count because they are transient modifications, not passed down to offspring?
Then this isnt epigenetics either. The second we use therapies to alter ‘epigenetic profiles’, they are not epigenetics anymore. They arent inherited. And how do you tell the epigenetics markers you got from Mom and Dad, vs the epigenetic markers you got from your environment or food or diseases?
… Or is ‘epigenetics’ really just a fancy word for transcription regulation?