CREB Regulation of Long-Term Associative Memory and Reproductive Aging in Caenorhabditis elegans

Abstract

The transcription factor CREB plays an important role in regulating a diverse array of biological processes, and a multitude of signal transduction pathways converge on CREB-mediated transcriptional activation. However, there is still no clear understanding of how CREB is able to distinguish between different signals to activate specific transcriptional programs, and the identities of CREB’s transcriptional targets in many of the biological processes it regulates remain unknown. Presented here is a characterization of CREB activity in two important biological processes, long-term memory and reproductive aging, in the nematode Caenorhabditis elegans, a system offering unique advantages for studying these traits. We identify the set of genes regulated by CREB specifically during memory formation following an associative learning task and use whole-genome transcriptional analysis to uncover potential mechanisms for CREB’s ability discriminate between its memory-related and other functions. These mechanisms include a potential transcription factor cascade mediated by the POU-domain transcription factor UNC-86 and the segregation of memory-related activity into a previously uncharacterized neuron-specific isoform of CREB, CREB-G. We also uncover a novel role for CREB in regulating reproductive longevity in C. elegans, and use a computational approach to determine that CREB mutants have transcriptional similarity to known reproductive mutants.