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• W2904505907 abstract "The brain-derived neurotrophic factor (BDNF) is a key player in brain functions such as synaptic plasticity, stress, and behavior. Its gene structure in rodents contains 8 untranslated exons (I to VIII) whose expression is finely regulated and which spliced onto a common and unique translated exon IX. Altered Bdnf expression is associated with many pathologies such as depression, Alzheimer’s disease and addiction. Through binding to glucocorticoid receptor (GR), glucocorticoids play a pivotal role for stress responses, mood and neuronal plasticity. We recently showed in neuronal primary culture and in the immortalized neuronal-like BZ cells that GR repressed Bdnf expression, notably the bdnf exon IV containing mRNA isoform (Bdnf4) via GR binding to a short 275-bp sequence of Bdnf promoter. Herein, we demonstrate by transient transfection experiments and mutagenesis in BZ cells that GR interacts with an early growth response protein 1 (EGR1) response element (EGR-RE) located in the transcription start site of Bdnf exon IV promoter. Using Chromatin Immunoprecipitation, we find that both GR and EGR1 bind to this promoter sequence in a glucocorticoid-dependent manner and demonstrate by co-immunoprecipitation that GR and EGR1 are interacting physically. Interestingly, EGR1 has been widely characterized as a regulator of brain plasticity. In conclusion, we deciphered a mechanism by which GR downregulates Bdnf expression, identifying a novel functional crosstalk between glucocorticoid pathways, immediate early growth response proteins and Bdnf. As all these factors are well-recognized germane for brain pathophysiology, these findings may have significant implications in neurosciences as well as in therapeutics." @default.
• W2904505907 created "2018-12-22" @default.
• W2904505907 creator A5011090841 @default.
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• W2904505907 creator A5063718814 @default.
• W2904505907 creator A5073621488 @default.
• W2904505907 date "2019-02-01" @default.
• W2904505907 modified "2023-10-03" @default.
• W2904505907 title "Crosstalk Between Glucocorticoid Receptor and Early-growth Response Protein 1 Accounts for Repression of Brain-derived Neurotrophic Factor Transcript 4 Expression" @default.
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• W2904505907 doi "https://doi.org/10.1016/j.neuroscience.2018.12.012" @default.
• W2904505907 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30578973" @default.
• W2904505907 hasPublicationYear "2019" @default.
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