RT Journal Article
SR Electronic
T1 cAMP Response Element-Binding Protein Is a Primary Hub of Activity-Driven Neuronal Gene Expression
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 18237
OP 18250
DO 10.1523/JNEUROSCI.4554-11.2011
VO 31
IS 50
A1 Eva Benito
A1 Luis M. Valor
A1 Maria Jimenez-Minchan
A1 Wolfgang Huber
A1 Angel Barco
YR 2011
UL http://www.jneurosci.org/content/31/50/18237.abstract
AB 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.