title: Activation-induced cytidine deaminase regulates activity-dependent BDNF expression in post-mitotic cortical neurons.
abstract: 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 mRNA expression, which correlated with a reduction in DNA methylation within the BDNF P4 promoter. Lentiviral-mediated knockdown of AID disrupted these effects and inhibited BDNF exon IV mRNA expression, an effect that was associated with decreased cAMP response element-binding protein occupancy within the BDNF P4 promoter. Thus, together with other epigenetic mechanisms, AID plays a key role in regulating activity-dependent BDNF expression in post-mitotic cortical neurons.
authors.affiliation: Psychiatric Epigenomics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, Qld, 4072, Australia.
authors.forename: Vikram S
authors.initials: VS
authors.lastname: Ratnu
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Bredy
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002540:Cerebral Cortex / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D003564:Cytidine Deaminase / Q000235:genetics*; D019175:DNA Methylation; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D008938:Mitosis; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D012333:RNA, Messenger; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase
keywords: AID; BDNF; DNA methylation; mice; post-mitotic cortical neurons