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

TitleGenome-wide functional analysis of CREB/long-term memory-dependent transcription reveals distinct basal and memory gene expression programs.
Publication TypeJournal Article
Year of Publication2015
AuthorsLakhina V, Arey RN, Kaletsky R, Kauffman A, Stein G, Keyes W, Xu D, Murphy CT
JournalNeuron
Volume85
Issue2
Pagination330-45
Date Published2015 Jan 21
ISSN1097-4199
KeywordsAnimals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Cyclic AMP Response Element-Binding Protein, Gene Expression Profiling, Gene Expression Regulation, Gene Expression Regulation, Developmental, Hippocampus, Learning, Memory, Memory, Long-Term, Neurons, Transcription Factors
Abstract

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.

DOI10.1016/j.neuron.2014.12.029
Alternate JournalNeuron
Full Text
PubMed ID25611510
PubMed Central IDPMC4340687
Grant ListF32 AG046106 / AG / NIA NIH HHS / United States
R01 AG034446 / AG / NIA NIH HHS / United States