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Activation‐induced cytidine deaminase regulates activity‐dependent BDNF expression in post‐mitotic cortical neurons
Author(s) -
Ratnu Vikram S.,
Wei Wei,
Bredy Timothy W.
Publication year - 2014
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12678
Subject(s) - cytidine deaminase , cytidine , activation induced (cytidine) deaminase , microbiology and biotechnology , cortical neurons , mitosis , chemistry , neuroscience , biology , biochemistry , gene , enzyme , genetics , immunoglobulin class switching , b cell , antibody
Activity‐dependent gene expression depends, in part, on transcriptional regulation that is coordinated by rapid changes in the chromatin landscape as well as the covalent modification of DNA . Here we demonstrate that the expression of brain‐derived neurotrophic factor ( BDNF ), a gene that is critically involved in neural plasticity and subject to epigenetic regulation, is regulated by the RNA / DNA editing enzyme, activation‐induced cytidine deaminase ( AID ). Similar to previous reports, we observed an activity‐dependent induction of BDNF exon IV m RNA expression, which correlated with a reduction in DNA methylation within the BDNF P 4 promoter. Lentiviral‐mediated knockdown of AID disrupted these effects and inhibited BDNF exon IV m RNA expression, an effect that was associated with decreased c AMP response element‐binding protein occupancy within the BDNF P 4 promoter. Thus, together with other epigenetic mechanisms, AID plays a key role in regulating activity‐dependent BDNF expression in post‐mitotic cortical neurons.