PRC2

About 90% of the chemical marks that build up on our DNA with age land in one kind of region.

Regions run by a protein complex called PRC2.

Think of it as the switch that keeps the genes for other kinds of cells turned off.

Which is why it's about identity.

That's the right warning.

But the review's point is where the marks pile up, at the switches that guard a cell's identity.

Horvath noticed years ago that the sites gaining marks with age sit at targets of PRC2.

Which means the review is connecting the clock to Waddington's Valleys.

[laughs]

H2A lysine one hundred and nineteen ubiquitylation, uh, leads to the recruitment of PRC2 and, uh, H3K27 trimethylation to effec- uh, efficiently initiate a polycomb domain.

Yeah.

In the abstract of the paper, you mentioned that this was an unexpected discovery.

They just didn't really know what it was doing.

So we followed that up, and we, we analyzed, you know, where this, uh, CXXC domain protein was bringing PRC1, and we could show that it'd bring it to CpG islands.

That was already a first interesting hint at things might be different than we originally thought because PRC1 was generally thought to be brought to its sites in the genome through recognizing the product of PRC2, which is TriMethyl K27.

We'd identified a mechanism now where PRC1 could be brought to CpG islands.