Cell-Autonomous and Non-Cell-Autonomous Regulation of a Feeding State-Dependent Chemoreceptor Gene via MEF-2 and bHLH Transcription Factors

Autor: Alexander M. van der Linden, Jeremy J. Grubbs, Dominic Valdes, Aja McDonagh, Ari Winbush, Matthew Gruner
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Receptors
Neuropeptide
Cancer Research
Chemoreceptor
Nematoda
Gene Expression
Biochemistry
Animals
Genetically Modified
0302 clinical medicine
RNA interference
Receptors
Pituitary Hormone-Regulating Hormone
Animal Cells
Gene expression
Transcriptional regulation
Basic Helix-Loop-Helix Transcription Factors
Medicine and Health Sciences
Genetics (clinical)
Genetics
Regulation of gene expression
Neurons
Gene Expression Regulation
Developmental
Animal Models
Chemoreceptor Cells
Cell biology
Nucleic acids
Genetic interference
Epigenetics
Cellular Types
Anatomy
Sequence Analysis
Signal Transduction
Research Article
Mef2
Sensory Receptor Cells
lcsh:QH426-470
Biology
Research and Analysis Methods
03 medical and health sciences
Model Organisms
Sequence Motif Analysis
Animals
Gene Regulation
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Molecular Biology Techniques
Sequencing Techniques
Transcription factor
Molecular Biology
Ecology
Evolution
Behavior and Systematics
Binding Sites
Organisms
Biology and Life Sciences
Cell Biology
Invertebrates
Gastrointestinal Tract
lcsh:Genetics
030104 developmental biology
Cellular Neuroscience
Caenorhabditis
TFEB
RNA
Sensory Neurons
Digestive System
030217 neurology & neurosurgery
Transcription Factors
Neuroscience
Zdroj: PLoS Genetics, Vol 12, Iss 8, p e1006237 (2016)
PLoS Genetics
ISSN: 1553-7404
1553-7390
Popis: Food and feeding-state dependent changes in chemoreceptor gene expression may allow Caenorhabditis elegans to modify their chemosensory behavior, but the mechanisms essential for these expression changes remain poorly characterized. We had previously shown that expression of a feeding state-dependent chemoreceptor gene, srh-234, in the ADL sensory neuron of C. elegans is regulated via the MEF-2 transcription factor. Here, we show that MEF-2 acts together with basic helix-loop-helix (bHLH) transcription factors to regulate srh-234 expression as a function of feeding state. We identify a cis-regulatory MEF2 binding site that is necessary and sufficient for the starvation-induced down regulation of srh-234 expression, while an E-box site known to bind bHLH factors is required to drive srh-234 expression in ADL. We show that HLH-2 (E/Daughterless), HLH-3 and HLH-4 (Achaete-scute homologs) act in ADL neurons to regulate srh-234 expression. We further demonstrate that the expression levels of srh-234 in ADL neurons are regulated remotely by MXL-3 (Max-like 3 homolog) and HLH-30 (TFEB ortholog) acting in the intestine, which is dependent on insulin signaling functioning specifically in ADL neurons. We also show that this intestine-to-neuron feeding-state regulation of srh-234 involves a subset of insulin-like peptides. These results combined suggest that chemoreceptor gene expression is regulated by both cell-autonomous and non-cell-autonomous transcriptional mechanisms mediated by MEF2 and bHLH factors, which may allow animals to fine-tune their chemosensory responses in response to changes in their feeding state.
Author Summary Plasticity in chemoreceptor gene expression may be a simple strategy by which an animal can modulate its chemosensory responses in changing external and internal state conditions. However, the transcriptional mechanisms required for these chemoreceptor gene expression changes are poorly understood. Here, we describe the identification of a transcriptional module(s) consisting of MEF-2 and basic helix-loop-helix (bHLH) transcription factors and their cognate binding sites in Caenorhabditis elegans that act together in ADL sensory neurons to properly regulate expression of a feeding-state dependent chemoreceptor gene. We also showed that chemoreceptor gene expression in ADL neurons are regulated remotely by bHLH factors acting in the intestine through an insulin-mediated signaling pathway, implying a sensory neuron-gut interaction for modulating chemoreceptor gene expression as a function of feeding state. This work describes transcriptional mechanisms mediated by MEF-2 and bHLH factors by which the expression of individual chemoreceptor genes in C. elegans are changed in response to changes in feeding state conditions.
Databáze: OpenAIRE
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