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 Pten, an inhibitor of PI3K-AKT-mTOR signaling, which occurred concurrently with increases in PTEN expression. CRISPR-dCas9 mediated upregulation of the H2Aubi ligase, Ring1b, in the amygdala enhanced contextual memory. These results suggest that decreases in transcriptionally repressive H2Aubi in the amygdala functions to constrain fear memory strength.