Acetylation of histone proteins by histone acetyltransferases (HATs), and the resultant change in gene expression, is a well-established mechanism necessary for long-term memory (LTM) consolidation, which is not required for short-term memory (STM). However, we previously demonstrated that the HAT p300/CBP-associated factor (PCAF) also influences hippocampus (HPC)-dependent STM in male rats. In addition to their epigenetic activity, HATs acetylate nonhistone proteins involved in nongenomic cellular processes, such as estrogen receptors (ERs). Given that ERs have rapid, nongenomic effects on HPC-dependent STM, we investigated the potential interaction between ERs and PCAF for STM mediated by the dorsal hippocampus (dHPC). Using a series of pharmacological agents administered directly into the dHPC, we reveal a functional interaction between PCAF and ERα in the facilitation of short-term object-in-place memory in male but not female rats. This interaction was specific to ERα, while ERβ agonism did not enhance STM. It was further specific to dHPC STM, as the effect was not present in the dHPC for LTM or in the perirhinal cortex. Further, while STM required local (i.e., dHPC) estrogen synthesis, the facilitatory interaction effect appeared independent of estrogens. Finally, western blot analyses demonstrated that PCAF activation in the dHPC rapidly (5 min) activated downstream estrogen-related cell signaling kinases (c-Jun N-terminal kinase and extracellular signal-related kinase). Collectively, these findings indicate that PCAF, which is typically implicated in LTM through epigenetic processes, also influences STM in the dHPC, possibly via nongenomic ER activity. Critically, this novel PCAF–ER interaction might exist as a male-specific mechanism supporting STM.

组蛋白乙酰转移酶 (HAT) 对组蛋白的乙酰化以及由此产生的基因表达变化是长期记忆 (LTM) 巩固所必需的成熟机制，而短期记忆 (STM) 则不需要。然而，我们之前证明 HAT p300/CBP 相关因子 (PCAF) 也会影响雄性大鼠海马 (HPC) 依赖性 STM。除了表观遗传活性外，HAT 还能乙酰化参与非基因组细胞过程的非组蛋白，例如雌激素受体 (ER)。鉴于 ER 对 HPC 依赖性 STM 具有快速的非基因组效应，我们研究了 ER 和 PCAF 之间对于背海马 (dHPC) 介导的 STM 的潜在相互作用。使用直接给予 dHPC 的一系列药物，我们揭示了 PCAF 和 ERα 之间的功能相互作用，促进雄性大鼠而非雌性大鼠的短期物体记忆。这种相互作用是 ERα 特有的，而 ERβ 激动剂不会增强 STM。它对 dHPC STM 更具有特异性，因为 LTM 的 dHPC 或鼻周皮层中不存在这种效应。此外，虽然STM需要局部（即dHPC）雌激素合成，但促进相互作用效应似乎与雌激素无关。最后，蛋白质印迹分析表明，dHPC 中的 PCAF 激活迅速（5 分钟）激活下游雌激素相关细胞信号激酶（c-Jun N 末端激酶和细胞外信号相关激酶）。总的来说，这些发现表明 PCAF 通常通过表观遗传过程参与 LTM，也可能通过非基因组 ER 活性影响 dHPC 中的 STM。重要的是，这种新颖的 PCAF-ER 相互作用可能作为支持 STM 的男性特异性机制而存在。