Live-cell DNMT3A "catalysome" mapping using engineered methyl-transfer pathways.
Engineered DNMT3A enables live-cell mapping of methylation activity, revealing distinct roles at genomic features in mammalian embryonic stem cells.
- Why it matters: Understanding the specific contributions of DNA methyltransferases like DNMT3A in native cellular contexts is limited, hindering insights into epigenetic regulation during development.
- What they did: Using structure-guided engineering, researchers modified DNMT3A to transfer azide tags from synthetic cofactors, allowing genome-wide mapping of its activity in live mouse embryonic stem cells through biocatalysis and metabolic strategies.
- The result: The approach uncovered opposing DNMT3A and TET activities at key genomic regions and highlighted DNMT3A’s enrichment at centromeric satellites, enabling precise, time-resolved studies of DNA methylation dynamics in physiological conditions.