CRTC1 Nuclear Translocation Following Learning Modulates Memory Strength via Exchange of Chromatin Remodeling Complexes on the Fgf1 Gene.
CRTC1 Nuclear Translocation Following Learning Modulates Memory Strength via Exchange of Chromatin Remodeling Complexes on the Fgf1 Gene.
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学习后的CRTC1核转运通过在FGF1基因上的染色质重塑复合物的交换来调节记忆力。
DOI：
10.1016/j.celrep.2016.12.052
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发表时间：
2017-01-10
期刊：
影响因子：
8.8
通讯作者：
Shumyatsky GP
中科院分区：
文献类型：
--
作者：
Uchida S;Teubner BJW;Hevi C;Hara K;Kobayashi A;Dave RM;Shintaku T;Jaikhan P;Yamagata H;Suzuki T;Watanabe Y;Zakharenko SS;Shumyatsky GP
记忆是由突触到核的通讯形成的，这种通讯导致基因转录的调节，但参与这种通讯的信号通路的身份和组织逻辑仍不清楚。在这里，我们发现转录因子CRTC1是海马区持续基因转录和记忆强度的关键决定因素。在联想学习之后，突触定位的CRTC1被转移到细胞核，并以一种活性依赖的方式调节Fgf1b的转录。经过弱训练和强训练后，HDAC3-N-COR辅阻遏子复合体离开Fgf1b启动子和一个涉及易位CRTC1、磷酸化CREB和组蛋白乙酰转移酶CBP的复合体，诱导瞬时转录。强大的训练后来取代了CBP的KAT5，这一过程依赖于CRTC1，但不依赖于CREB的磷酸化。这反过来会导致Fgf1b转录和记忆的长期增强。因此，记忆的强度依赖于染色质的活动变化和对特定CREB/CRTC1基因靶点的基因转录的时间调节。
Memory is formed by synapse-to-nucleus communication that leads to regulation of gene transcription, but the identity and organizational logic of signaling pathways involved in this communication remain unclear. Here we find that the transcription factor CRTC1 is a critical determinant of sustained gene transcription and memory strength in the hippocampus. Following associative learning, synaptically localized CRTC1 is translocated to the nucleus and regulates Fgf1b transcription in an activity-dependent manner. After both weak and strong training, the HDAC3–N-CoR corepressor complex leaves the Fgf1b promoter and a complex involving the translocated CRTC1, phosphorylated CREB and histone acetyltransferase CBP induces transient transcription. Strong training later substitutes KAT5 for CBP, a process that is dependent on CRTC1, but not on CREB phosphorylation. This in turn leads to long-lasting Fgf1b transcription and memory enhancement. Thus, memory strength relies on activity-dependent changes in chromatin and temporal regulation of gene transcription on specific CREB/CRTC1 gene targets.