Parra-Damas, ArnaldoRubió-Ferrarons, LauraShen, JieSaura, Carlos A.2018-01-182017Parra-Damas, Arnaldo, Laura Rubió-Ferrarons, Jie Shen, and Carlos A. Saura. 2017. “CRTC1 mediates preferential transcription at neuronal activity-regulated CRE/TATA promoters.” Scientific Reports 7 (1): 18004. doi:10.1038/s41598-017-18215-y. http://dx.doi.org/10.1038/s41598-017-18215-y.http://nrs.harvard.edu/urn-3:HUL.InstRepos:34651730Gene expression mediated by the transcription factor cAMP-responsive element-binding protein (CREB) is essential for a wide range of brain processes. The transcriptional coactivartor CREB-regulated transcription coactivator-1 (CRTC1) is required for efficient induction of CREB target genes during neuronal activity. However, the mechanisms regulating induction of specific CREB/CRTC1-dependent genes during neuronal activity remain largely unclear. Here, we investigated the molecular mechanisms regulating activity-dependent gene transcription upon activation of the CREB/CRTC1 signaling pathway in neurons. Depolarization and cAMP signals induce preferential transcription of activity-dependent genes containing promoters with proximal CRE/TATA sequences, such as c-fos, Dusp1, Nr4a1, Nr4a2 and Ptgs2, but not genes with proximal CRE/TATA-less promoters (e.g. Nr4a3, Presenilin-1 and Presenilin-2). Notably, biochemical and chromatin immunoprecipitation analyses reveal constitutive binding of CREB to target gene promoters in the absence of neuronal activity, whereas recruitment of CRTC1 to proximal CRE/TATA promoters depends on neuronal activity. Neuronal activity induces rapid CRTC1 dephosphorylation, nuclear translocation and binding to endogenous CREB. These results indicate that neuronal activity induces a preferential binding of CRTC1 to the transcriptional complex in CRE/TATA-containing promoters to engage activity-dependent transcription in neurons.en-USJournal Article2018-01-1810.1038/s41598-017-18215-y