title: cAMP response element-binding protein is a primary hub of activity-driven neuronal gene expression.
abstract: Long-lasting forms of neuronal plasticity require de novo gene expression, but relatively little is known about the events that occur genome-wide in response to activity in a neuronal network. Here, we unveil the gene expression programs initiated in mouse hippocampal neurons in response to different stimuli and explore the contribution of four prominent plasticity-related transcription factors (CREB, SRF, EGR1, and FOS) to these programs. Our study provides a comprehensive view of the intricate genetic networks and interactions elicited by neuronal stimulation identifying hundreds of novel downstream targets, including novel stimulus-associated miRNAs and candidate genes that may be differentially regulated at the exon/promoter level. Our analyses indicate that these four transcription factors impinge on similar biological processes through primarily non-overlapping gene-expression programs. Meta-analysis of the datasets generated in our study and comparison with publicly available transcriptomics data revealed the individual and collective contribution of these transcription factors to different activity-driven genetic programs. In addition, both gain- and loss-of-function experiments support a pivotal role for CREB in membrane-to-nucleus signal transduction in neurons. Our data provide a novel resource for researchers wanting to explore the genetic pathways associated with activity-regulated neuronal functions.
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández/Consejo Superior de Investigaciones Científicas, Sant Joan d'Alacant, 03550 Alicante, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Benito
authors.forename: Luis M
authors.initials: LM
authors.lastname: Valor
authors.forename: Maria
authors.initials: M
authors.lastname: Jimenez-Minchan
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Huber
authors.forename: Angel
authors.initials: A
authors.lastname: Barco
mesh_terms: D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism*; D051379:Mice; D009473:Neuronal Plasticity / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000235:genetics*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D026362:Serum Response Factor