biostudies-literatureJarome TJNIMH NIH HHSNational Institute of Mental HealthNINDS NIH HHSNIGMS NIH HHS1176-1187https://www.ebi.ac.uk/biostudies/studies/S-EPMC8178164biostudies-literatureUnknown89(12)<h4>Background</h4>Posttranslational histone modifications play a critical role in the regulation of gene transcription underlying synaptic plasticity and memory formation. One such epigenetic change is histone ubiquitination, a process that is mediated by the ubiquitin-proteasome system in a manner similar to that by which proteins are normally targeted for degradation. However, histone ubiquitination mechanisms are poorly understood in the brain and in learning. In this article, we describe a new role for the ubiquitin-proteasome system in histone crosstalk, showing that learning-induced monoubiquitination of histone H2B (H2Bubi) is required for increases in the transcriptionally active H3 lysine 4 trimethylation (H3K4me3) mark at learning-related genes in the hippocampus.<h4>Methods</h4Biological psychiatryUbiquitination of Histone H2B by Proteasome Subunit RPT6 Controls Histone Methylation Chromatin Dynamics During Memory Formation.PMC8178164R56 MH097909K99 MH082106T32 GM008361T32 NS061788R01 MH097909R00 MH082106R25 NS089463T32 NS095775F30 NS100340Webb WMHatch KMNavabpour SButler AALubin FDPerez GAFarrell KWang JJarome TJMartin KHauser RMMcFadden TMusaus MfalseUbiquitination of Histone H2B by Proteasome Subunit RPT6 Controls Histone Methylation Chromatin Dynamics During Memory Formation.<h4>Background</h4>Posttranslational histone modifications play a critical role in the regulation of gene transcription underlying synaptic plasticity and memory formation. One such epigenetic change is histone ubiquitination, a process that is mediated by the ubiquitin-proteasome system in a manner similar to that by which proteins are normally targeted for degradation. However, histone ubiquitination mechanisms are poorly understood in the brain and in learning. In this article, we describe a new role for the ubiquitin-proteasome system in histone crosstalk, showing that learning-induced monoubiquitination of histone H2B (H2Bubi) is required for increases in the transcriptionally active H3 lysine 4 trimethylation (H3K4me3) mark at learning-related genes in the hippocampus.<h4>Methods</h42021-01-01T00:00:00Z2021 Jun2026-05-09T03:20:40.661Z2025-04-04T22:15:22.95ZS-EPMC81781643393488510.1016/j.biopsych.2020.12.029