Beyond 5mC: 6mA Joins the Epigenetic Cast

While we have traditionally focused on 5-methylcytosine DNA (5mC) methylation in the laboratory, we started exploring 6-methyladenine (6mA) some years ago with Pedro Romero Charria, the lab's second PhD student. The field was a bit messy since there have been high profile reports saying 6mA is present in all sorts of model systems, including mammals, plants or flies. However, this was also heavily contested. We decided to check for ourselves, since the scattered reports from ciliates, early diverging fungi and the green algae Chlamydomonas suggested that 6mA was probably more widespread. In a new publication in Nature Genetics, we trace the evolution of 6mA to the Last Eukaryotic Common Ancestor, and find that in contrast to 5mC, its patterns are surprisingly conserved throughout evolution. Still, 6mA and its main enzymatic complement, the AMT1 methyltransferase complex, have been lost in many branches of the tree of life, including all complex multicellular lineages (animals, plants, fungi, brown and red algae). Importantly, 6mA is a integral part of the ancestral eukaryotic chromatin, as it is inheritable (deposited in symmetric ApT dinucleotides) and co-localises with H3K4me3. In this regard, multicellular lineages are simpler than their unicellular ancestors, which is a fascinating question we want to explore.

We also got to write a Research Briefing summarising the findings and telling a bit of the behind the paper story.

Diversity of eukaryotes profiled in the study. Expansion microscopy images with DNA (blue) and microtubules (magenta) stained. Pictures and composition courtesy to Dr. Omaya Dudin.

Based on the discoveries of this paper, we got granted a Wellcome Trust Discovery Award to keep exploring 6mA evolution. There are many mysteries that still surround this mark, so if you're curious and want to join our quest or collaborate, feel free to reach out!