# That's Not How Epigenetic Modifications Work

Ask an epigenetics researcher what they study, and the standard story you'll hear goes something like this...

"Sometimes a little methyl group (i.e. -CH3) gets stuck on the side of a strand of DNA. Turns out these guys are pretty important! They're copied over when cells replicate, so they stick around long-term, and they can activate or repress (usually repress) nearby genes on the DNA strand. In particular, different types of cells all have the same DNA code, but *something* has to be different in order for the cells to "remember" what type they are and behave differently. And sure enough, those methyl modifications differ across cell types! They're like an extra information storage mechanism, on top of the DNA, which can encode things like cell type and make different cell types behave differently, among other forms of memory."

That story is wrong. Many of the details are correct, but there's one crucial mistake, and once we correct that mistake we end up with a very different mental picture.

The mistake: methyl groups usually do not stick around long-term; they turn over regularly. Here are [two](https://www.nature.com/articles/s41467-020-16354-x) [studies](https://pmc.ncbi.nlm.nih.gov/articles/PMC3335907/) which measured the turnover. Turnover timescale varies by location on the DNA strand, but turnover every few days is typical.

With that in mind, here's how I'd describe the way methyl modifications actually work...

"Sometimes chemical signals have multiple steady states - for instance, maybe A suppresses B and B suppresses A, such that both (high A, low B) and (low A, high B) are stable. Turns out chemical subsystems with multiple steady states are pretty important! Since the state is steady, it can stick around long-term, and even stick around when a cell replicates. In particular, different types of cells all have the same DNA code, but *something* has to be different in order for the cells to "remember" what type they are and behave differently. Subsystems with multiple steady states play that role! They're like an extra information storage mechanism, on top of the DNA, which can encode things like cell type and make different cell types behave differently.

And it turns out that methyl modifications, along with things like proteins and small molecules and all the other typical chemical types in a cell, are among the chemicals which can be part of such a subsystem. In fact, methyl modifications are particularly well suited to this role, because they can be highly redundant at relatively low metabolic cost: there can be methyl modifications at many sites which all 'say the same thing' about the cell state, making the memory quite robust!"

Personally, I ran into this while studying [aging](https://www.lesswrong.com/posts/ui6mDLdqXkaXiDMJ5/core-pathways-of-aging). If we imagine that methyl groups stick around indefinitely, then (at least in long-lived cells) they're a prime candidate for mediating age-related changes. But if the methyl groups are instead part of a dynamic equilibrium, especially with high redundancy (and therefore stability), then that's a whole different situation.