Glucocorticoid receptor and myocyte enhancer factor 2 cooperate to regulate the expression of c-JUN in a neuronal context

Autor: Niels Speksnijder, Nicole A. Datson, Michael Didriksen, E. Ronald de Kloet, Kenneth Vielsted Christensen
Rok vydání: 2012
Předmět:
Mef2
animal structures
Proto-Oncogene Proteins c-jun
Repressor
Down-Regulation
MADS Domain Proteins
Mice
Inbred Strains
Glucocorticoid receptor
Biology
Hippocampus
PC12 Cells
Dexamethasone
Article
03 medical and health sciences
Cellular and Molecular Neuroscience
Mice
0302 clinical medicine
Receptors
Glucocorticoid
Myocyte enhancer factor 2
Animals
Phosphorylation
Enhancer
Transcription factor
Glucocorticoids
030304 developmental biology
Regulation of gene expression
Neurons
0303 health sciences
Gene knockdown
Neuronal Plasticity
MEF2 Transcription Factors
c-jun
c-JUN
General Medicine
musculoskeletal system
Molecular biology
Rats
Animals
Newborn
Gene Expression Regulation
Myogenic Regulatory Factors
Gene Knockdown Techniques
embryonic structures
cardiovascular system
tissues
030217 neurology & neurosurgery
PC-12 cells
Zdroj: Journal of Molecular Neuroscience
Journal of Molecular Neuroscience, 48(1), 209-218. HUMANA PRESS INC
ISSN: 1559-1166
Popis: The glucocorticoid receptor (GR) and myocyte enhancer factor 2 (MEF2) are transcription factors involved in neuronal plasticity. c-JUN, a target gene of GR and MEF2, plays a role in regulating both synaptic strength and synapse number. The aim of this study was to investigate the nature of this dual regulation of c-JUN by GR and MEF2 in a neuronal context. First, we showed that GR mediates the dexamethasone-induced suppression of c-JUN mRNA expression. Next, we observed that GR activation resulted in an increase in phosphorylation of MEF2, a post-translational modification known to change MEF2 from a transcriptional enhancer to a repressor. In addition, we observed an enhanced binding of MEF2 to genomic sites directly upstream of the c-JUN gene upon GR activation. Finally, in primary hippocampal neuronal cultures, knockdown of MEF2 not only reduced c-JUN expression levels but abolished GR regulation of c-JUN expression. This suggests that MEF2 is necessary for GR regulation of c-JUN. In conclusion, for the first time, we show that activated GR requires MEF2 to regulate c-JUN. At the same time, GR influences MEF2 activity and DNA binding. These results give novel insight into the molecular interplay of GR and MEF2 in the control of genes important for neuronal plasticity. Electronic supplementary material The online version of this article (doi:10.1007/s12031-012-9809-2) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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