ABSTRACT
The expression of individual chemoreceptor (CR) genes in Caenorhabditis elegans is regulated by multiple environmental and developmental cues, possibly enabling C. elegans to modulate its sensory responses. We had previously shown that KIN-29, a member of the salt-inducible kinase family, acts in a subset of chemosensory neurons to regulate the expression of CR genes, body size and entry into the alternate dauer developmental stage. Here, we show that KIN-29 regulates these processes by phosphorylating the HDA-4 class II histone deacetylase (HDAC) and inhibiting the gene repression functions of HDA-4 and an MEF-2 MADS domain transcription factor. MEF-2 binds directly to the CR gene regulatory sequences, and is required only to repress but not activate CR gene expression. A calcineurin phosphatase antagonizes the KIN-29/MEF-2-regulated pathway to modulate levels of CR gene expression. Our results identify KIN-29 as a new regulator of MEF2/HDAC functions in the nervous system, reveal cell-specific mechanisms of action of this pathway in vivo and demonstrate remarkable complexity in the regulation of CR gene expression in C. elegans.
Subject(s)
Caenorhabditis elegans Proteins/physiology , Chemoreceptor Cells/metabolism , Histone Deacetylases/physiology , MADS Domain Proteins/physiology , Protein Serine-Threonine Kinases/physiology , Transcription Factors/physiology , Animals , Animals, Genetically Modified , Binding Sites , Caenorhabditis elegans , Caenorhabditis elegans Proteins/genetics , Calcineurin/physiology , Calcium Signaling , Gene Expression Regulation , Histone Deacetylases/genetics , MADS Domain Proteins/genetics , Models, Biological , Mutation , Protein Binding , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Transcription Factors/geneticsABSTRACT
Regulation of chemoreceptor gene expression in response to environmental or developmental cues provides a mechanism by which animals can alter their sensory responses. Here we demonstrate a role for the daf-7 TGF-beta pathway in the regulation of expression of a subset of chemoreceptor genes in Caenorhabditis elegans. We describe a novel role of this pathway in maintaining receptor gene expression in the adult and show that the DAF-4 type II TGF-beta receptor functions cell-autonomously to modulate chemoreceptor expression. We also find that the alteration of receptor gene expression in the ASI chemosensory neurons by environmental signals, such as levels of a constitutively produced pheromone, may be mediated via a DAF-7-independent pathway. Receptor gene expression in the ASI and ASH sensory neurons appears to be regulated via distinct mechanisms. Our results suggest that the expression of individual chemoreceptor genes in C. elegans is subject to multiple modes of regulation, thereby ensuring that animals exhibit the responses most appropriate for their developmental stage and environmental conditions.
