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. Dorsal hippocampus mRNA profiles of 2-4 months old male WT and CBP KIX/KIX mice.研究目的：我们采用携带可阻断磷酸化CREB（Ser133）结合突变的CBPKIX/KIX小鼠，探究CBP KIX结构域（CBP KIX domain）在海马记忆与基因表达调控中的功能。 实验方法：我们对经过海马依赖性记忆训练的CBPKIX/KIX小鼠与野生型（WT）同窝仔鼠开展了总RNA测序（total RNA sequencing）。 实验结果：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CBPKIX/KIX小鼠中CREB与CLOCK靶基因存在表达失调，且节律相关基因出现下调。 研究结论：本研究明确了CBP转录共激活在记忆过程中的靶标，并阐明了CBP KIX结构域在体内对昼夜节律的调控作用，从而为理解CBP KIX结构域的生物学意义提供了新见解。本数据集包含2-4月龄雄性野生型与CBP KIX/KIX小鼠的背侧海马mRNA表达谱。