“Newborn” (or de novo) DNA sequences come into this world just like newborn human babies—naked. So, how do new sequences get their DNA methylation on? Researchers from the Chinese Academy of Sciences say they’ve figured out what happens after the histones settle in: H3 tails that lack methylation at K4 bind to and activate de novo methyltransferases, priming them to methylate nearby DNA.
De novo methyltransferases (Dnmt3s) directly or indirectly bind to histone tails in order to methylate DNA—that much was known. But the Chinese team went a step further, wondering if the histone tails also regulate Dnmt3 activity. Here’s what they found:
- Dnmt3a activity increased (by up to 8-fold!) in vitro when H3 tail peptides were di-, mono-, or unmethylated on K4, but it didn’t increase when the peptides were tri-methylated.
- Dnmt3a had to bind to H3 tails before getting activated.
- Certain mutations in the Dnmt3a plant homeodomain and in its catalytic site mess up the activation, but still allow it to bind to H3—so these steps are separate.
The researchers say these data show that after Dnmt3a is recruited to chromatin, it binds to unmethylated (or low-methylated) H3 tails at K4. Only then is Dnmt3a activated to methylate nearby cytosines.
Check out the brand spanking-new data at Cell Research, May 2011.