LSI External Seminar - Francis Stewart

Methylation of histone 3 lysine 4 is the most conserved aspect of eukaryotic epigenetics and a universal characteristic of active chromatin. Almost all active Pol II promoters are trimethylated on adjacent nucleosomes. Mammals have six H3K4 methyltransferases of the Set1/Trithorax class, and all six are required during development, however for different reasons. The four Trithorax homologs, MLL1-4, are very large proteins including the largest known nucleoplasmic protein, MLL4. Notably, the requirement for MLL2 in neuroectodermal differentiation correlates with its ability to tether chromatin rather than its H3K4 methylation activity. Potentially the MLLs primarily exert their activities as epigenetic maintenance factors through tethering the 3D genome and H3K4 methylation is a complementary activity.