Splitting up work amongst the team is always a sound strategy for success. We’ve seen that the TET family likes to divide it’s labour and now, not so suprisingly, the ever so famous DNA methyltransferases have also been caught working smart.
Researchers from the Center for Individualized Medicine at the Mayo Clinic used acute and combined depletions of DNMTs in a pluripotent human tumor cell line and some omics to study DNMT isoform functions in the finest of detail. Here’s what they found:
- When DNMT3B is on the scene the methylation profile is related to the initiation of differentiation.
- DNMT3B depletion showed a strange pattern of hypermethylation by standard bisulfite conversion, but oxidative bisulfite revealed that this increase was mainly due to increased recruitment of TETs and 5hmC dynamics.
- It seems that DNMT1 and DNMT3B are caught in a co-regulatory civil war over certain gene bodies, antagonizing each other with 5mC and 5hmC in an inverse fashion, with a depletion of DNMT3B increasing the recruitment of TET.
- Genes hypermethylated from DNMT3B depletion correlate with highly expressed genes marked with H3K36me3.
- DNMT3B typically promotes non-CpG methylation, unless DNMT3L comes on the scene to sway the CpG versus non-CpG choice.
By using these clever combos the team ultimately reveals the functional targets of the DNMTs. This has potential clinical implications: by taking advantage of the specificity of the different isoforms towards certain methylation patterns through selective inhibition could allow generation of some desirable designer DNAm patterns.
Take a lesson from the DNMTs and learn how to efficiently divide your epigenomic labour in Cell Reports, November 2014