H2A.Z helps genes remember their history so we can remember ours.

Histone variant exchange is a novel epigenetic regulator of cognition. We speculate that H2A.Z, a variant of canonical histone H2A, exerts unique effects on transcription during distinct stages of memory formation, ultimately acting to maintain memory of previous transcriptional states and poise genes for re-activation. Hippocampus-dependent memory formation is initiated by transient expression of memory-related genes, which support the storage of recently acquired memories. Soon after, memories undergo systems consolidation, which transfers memories from the hippocampus to the cortex for long-term storage, and requires ongoing re-activation of memory-related genes. We speculate that learning-induced H2A.Z eviction from nucleosomes initially contributes to stimulus-induced transcriptional induction needed for the initial process of memory consolidation. During systems consolidation, we speculate that delayed incorporation of H2A.Z into nucleosomes of memory-related genes in the cortex is needed to poise genes for rapid re-activation, thus supporting the long-term process of memory stabilization.