Long-term synaptic plasticity and memory requires neuronal activity-induced gene expression regulated by the transcription factor cAMP-response element binding protein (CREB). CREB-dependent gene expression requires transcriptional coactivators, such as CREB binding protein (CBP/P300) and CREB-regulated transcription coactivator-1 (CRTC1). However, the specific gene programs regulated by CRTC1 during induction of neuronal activity remain unknown. Using chromatin immunoprecipitation sequencing (ChIP-seq), we analyzed the genome-wide occupancy profiles of CRTC1 in cultured neurons in both basal and stimulated conditions after treatment with forskolin and potassium chloride (FSK/KCl), which induces CRTC1 dephosphorylation, nuclear translocation and binding to promoter regions of target genes. We detected strong induction of CRTC1 occupancy in a subset of CREB target genes upon FSK/KCl treatment, including proximal promoter regions and distal regions comprising well-characterized neuronal activity-regulated enhancers. Interestingly, we identified activity-dependent binding of CRTC1 at genes mediating neuronal excitability and synaptic plasticity, including neurotransmitter receptors, synaptic proteins and transcriptional regulators. These results suggest that CRTC1 regulates gene programs supporting local synaptic plasticity and global neuronal excitability.

Host: Cell Signaling and apoptosis (VHIR)

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https://gencat.zoom.us/j/99144261702