Mll1 pioneers histone H3K4me3 deposition and promotes formation of CD8 T stem cell memory.

CD8 T cells with stem cell-like properties (T ) sustain adaptive immunity to intracellular pathogens and tumors. However, the developmental origins and chromatin regulatory factors (CRFs) that establish their differentiation are unclear. Using an RNA interference screen of all CRFs we discovered the histone methylase Mll1 was required during T cell receptor (TCR) stimulation for development of a T precursor state and mature memory (T ) cells, but not short-lived or transitory effector cell-like states, in response to viral infections and tumors.