Our latest paper shows a functional relationship between KDM5C and KMT2A in mice, providing a proof of principle for balancing a single writer-eraser pair to ameliorate their associated human disorders. This work was lead by lab alumna Christina Vallianatos for her PhD thesis, and key collaborators from the Tronson lab, the Dou lab, Neurodigitech, and others.
Despite opposite enzymatic activities, we found the two mouse models deficient for either Kmt2a or Kdm5c shared reduced dendritic spines and increased aggression. Double mutation of both Kmt2a and Kdm5c clearly reversed dendritic morphology, key behavioral traits including aggression, and partially corrected altered transcriptomes and H3K4me landscapes. Our study uncovers common yet mutually suppressive aspects of this writer-erase pair, which could be a new key therapeutic strategy.
Read the study here: