title: Genome-wide functional analysis of CREB/long-term memory-dependent transcription reveals distinct basal and memory gene expression programs.
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.
authors.affiliation: Department of Molecular Biology & LSI Genomics, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Vanisha
authors.initials: V
authors.lastname: Lakhina
authors.affiliation: Department of Molecular Biology & LSI Genomics, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Rachel N
authors.initials: RN
authors.lastname: Arey
authors.affiliation: Department of Molecular Biology & LSI Genomics, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Kaletsky
authors.affiliation: Department of Molecular Biology & LSI Genomics, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Kauffman
authors.affiliation: Department of Molecular Biology & LSI Genomics, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Geneva
authors.initials: G
authors.lastname: Stein
authors.affiliation: Department of Molecular Biology & LSI Genomics, Princeton University, Princeton, NJ 08544, USA.
authors.forename: William
authors.initials: W
authors.lastname: Keyes
authors.affiliation: Department of Molecular Biology & LSI Genomics, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Molecular Biology & LSI Genomics, Princeton University, Princeton, NJ 08544, USA. Electronic address: ctmurphy@princeton.edu.
authors.forename: Coleen T
authors.initials: CT
authors.lastname: Murphy
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006624:Hippocampus / Q000378:metabolism*; D007858:Learning; D008568:Memory; D057567:Memory, Long-Term; D009474:Neurons / Q000378:metabolism*; D014157:Transcription Factors
chemical_list: D029742:Caenorhabditis elegans Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D014157:Transcription Factors