Bae Yeeun, Venkat Harshini, Preveza Natalie, Turner Meagan, Jarome Timothy J
School of Animal Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, USA.
School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, USA.
Learn Mem. 2025 Mar 18;32(3). doi: 10.1101/lm.054092.125. Print 2025 Mar.
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 , an inhibitor of PI3K-AKT-mTOR signaling, which occurred concurrently with increases in PTEN expression. CRISPR-dCas9 mediated upregulation of the H2Aubi ligase, , in the amygdala enhanced contextual memory. These results suggest that decreases in transcriptionally repressive H2Aubi in the amygdala functions to constrain fear memory strength.
有证据表明，组蛋白H2B的单泛素化（一种基因转录增加的调节因子）在记忆形成中发挥作用。然而，作为转录抑制因子的组蛋白H2A的单泛素化（H2Aubi）是否参与记忆形成尚未得到研究。我们发现，恐惧条件反射后杏仁核中H2Aubi的整体水平和基因特异性水平均下降。在PI3K-AKT-mTOR信号通路的抑制剂作用下，H2Aubi减少，同时PTEN表达增加。CRISPR-dCas9介导的杏仁核中H2Aubi连接酶的上调增强了情境记忆。这些结果表明，杏仁核中转录抑制性H2Aubi的减少起到限制恐惧记忆强度的作用。
