Decreases in H2A monoubiquitination in the amygdala constrain fear memory formation

Evidence suggests a role for monoubiquitination of histone H2B, a regulator of increased gene transcription, in memory formation. However, whether monoubiquitination of histone H2A (H2Aubi), a transcriptional repressor, is involved in memory formation has not been explored. We found global and gene-specific decreases in H2Aubi in the amygdala following fear conditioning. H2Aubi decreased at <i>Pten</i>, an inhibitor of PI3K-AKT-mTOR signaling, which occurred concurrently with increases in PTEN expression. CRISPR-dCas9 mediated upregulation of the H2Aubi ligase, <i>Ring1b</i>, in the amygdala enhanced contextual memory. These results suggest that decreases in transcriptionally repressive H2Aubi in the amygdala functions to constrain fear memory strength.