The CBP KIX domain regulates long-term memory and circadian activity

Purpose: We investigated the function of the CBP KIX domain in hippocampal memory and gene expression using CBPKIX/KIX mice with mutations that prevent phospho-CREB (Ser133) binding. Method: We performed total RNA sequencing after training for hippocampus-dependent memory from CBP KIX/KIX and WT littermates. Results: Using an unbiased analysis of gene expression after training for hippocampus-dependent memory, we discovered dysregulation of CREB and CLOCK target genes and downregulation of circadian genes in CBPKIX/KIX mice. Conclusion: This study provides insight into the significance of the CBP KIX domain by defining targets of CBP transcriptional co-activation in memory and the role of the CBP KIX domain in vivo on circadian rhythms. Overall design: Dorsal hippocampus mRNA profiles of 2-4 months old male WT and CBP KIX/KIX mice.

研究目的：本研究利用携带可阻断磷酸化cAMP反应元件结合蛋白（CREB，Ser133）结合突变的CBP KIX/KIX小鼠，探究CBP KIX结构域（CBP KIX domain）在海马记忆与基因表达中的功能。实验方法：我们对CBP KIX/KIX小鼠与野生型（WT）同窝小鼠开展海马依赖性记忆训练后，进行总RNA测序。研究结果：通过对海马依赖性记忆训练后的基因表达进行无偏分析，我们发现CBP KIX/KIX小鼠中CREB与时钟基因（CLOCK）靶基因表达失调，且昼夜节律基因表达下调。研究结论：本研究通过明确CBP在记忆过程中的转录共激活靶点，以及阐释CBP KIX结构域在体内对昼夜节律的调控作用，为理解该结构域的生物学意义提供了新的见解。整体实验设计：针对2至4月龄雄性野生型（WT）及CBP KIX/KIX小鼠的背侧海马mRNA开展转录组表达谱分析。