Decreases in monoubiquitination of histone H2B is a critical regulator of age-related memory decline

We report a critical role of decreased monoubiquitination of H2B (H2Bubi) in age-related memory decline. We found that contextual fear conditioning in aged rats led to modest transcriptional changes in the hippocampus, which was correlated with impaired memory. Conversely, CRISPR-dCas9-mediated increases in the H2Bubi ligase, Rnf20, in the hippocampus improved memory in aged rats and resulted in a more robust transcriptome. Surprisingly, 18 genes upregulated with learning in the control group was also found in the rnf20 upregulation condition, though the later included more than 20 additional upregulated and 10 downregulated genes. These data suggest that upregulating H2Bubi in the aged hipocampus may improve memory by controlling transcriptional changes in a subset of memory critical genes Overall design: Male 22 month old Fischer ratss were injected into dorsal hippocampus CA1 region with CRISPR gRNA targeting Rnf20 alone or with dCas9-VPR. Four weeks later, animals were trained to contextual fear conditioning and the CA1 region (dorsal) was dissected, RNA collected via columns and used for RNA-seq analysis