Genome-wide occupancy of CRTC1 in neurons

Background: Gene expression regulated by the transcription factor cAMP-response element binding protein (CREB) is modulated by transcriptional coactivators such as CBP/P300 and CREB-regulated transcription coactivator-1 (CRTC1). However, the genome-wide occupancy profile of CRTC1 in neurons is unknown. Aim: We analyzed the genome-wide occupancy profiles of CRTC1 in primary cortical neurons in basal and stimulated conditions after treatment with forskolin and potassium chloride (FK), which induces CRTC1 dephosphorylation, nuclear translocation and binding to promoter regions of target genes (PMID: 29269871). Methods: 40 million reads per sample were quality-filtered and aligned to the reference genome (mm10) before input normalization, peak calling and annotation. Results: We identified strong induction of CRTC1 occupancy after treatment with FK at over 2,500 binding sites comprising proximal promoter regions and distal regions, including well-characterized neuronal activity-regulated enhancers (PMID: 20393465). Conclusions: Neuronal activity induces binding of CRTC1 to promoter and enhancer regions of target genes.