Genome-wide functional analysis of CREB/long-term memory-dependent transcription reveals distinct basal and memory gene expression programs

Induced CREB activity is a hallmark of long-term memory, but the full repertoire of CREB transcriptional targets required specifically for memory is not known in any system. To obtain a more complete picture of the mechanisms involved in memory, we combined memory training with genome-wide transcrip...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2015-01, Vol.85 (2), p.330-345
Main Authors: Lakhina, Vanisha, Arey, Rachel N, Kaletsky, Rachel, Kauffman, Amanda, Stein, Geneva, Keyes, William, Xu, Daniel, Murphy, Coleen T
Format: Article
Language:English
Subjects:
Animals
Caenorhabditis elegans
Caenorhabditis elegans Proteins - genetics
Caenorhabditis elegans Proteins - metabolism
Cyclic AMP Response Element-Binding Protein - genetics
Cyclic AMP Response Element-Binding Protein - metabolism
Gene expression
Gene Expression Profiling
Gene Expression Regulation - genetics
Gene Expression Regulation, Developmental - genetics
Genomes
Hippocampus - metabolism
Kinases
Learning
Mammals
Memory
Memory, Long-Term
Metabolism
Neurons - metabolism
Proteins
Recall
Rodents
Short term
Transcription Factors
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Summary:Induced CREB activity is a hallmark of long-term memory, but the full repertoire of CREB transcriptional targets required specifically for memory is not known in any system. To obtain a more complete picture of the mechanisms involved in memory, we combined memory training with genome-wide transcriptional analysis of C. elegans CREB mutants. This approach identified 757 significant CREB/memory-induced targets and confirmed the involvement of known memory genes from other organisms, but also suggested new mechanisms and novel components that may be conserved through mammals. CREB mediates distinct basal and memory transcriptional programs at least partially through spatial restriction of CREB activity: basal targets are regulated primarily in nonneuronal tissues, while memory targets are enriched for neuronal expression, emanating from CREB activity in AIM neurons. This suite of novel memory-associated genes will provide a platform for the discovery of orthologous mammalian long-term memory components.
ISSN:0896-6273
1097-4199
DOI:10.1016/j.neuron.2014.12.029