PMID- 26336984 OWN - NLM STAT- MEDLINE DCOM- 20160801 LR - 20181113 IS - 1559-2308 (Electronic) IS - 1559-2294 (Print) IS - 1559-2294 (Linking) VI - 10 IP - 10 DP - 2015 TI - Regulation of BDNF chromatin status and promoter accessibility in a neural correlate of associative learning. PG - 981-93 LID - 10.1080/15592294.2015.1090072 [doi] AB - Brain-derived neurotrophic factor (BDNF) gene expression critically controls learning and its aberrant regulation is implicated in Alzheimer's disease and a host of neurodevelopmental disorders. The BDNF gene is target of known DNA regulatory mechanisms but details of its activity-dependent regulation are not fully characterized. We performed a comprehensive analysis of the epigenetic regulation of the turtle BDNF gene (tBDNF) during a neural correlate of associative learning using an in vitro model of eye blink classical conditioning. Shortly after conditioning onset, the results from ChIP-qPCR show conditioning-dependent increases in methyl-CpG-binding protein 2 (MeCP2) and repressor basic helix-loop-helix binding protein 2 (BHLHB2) binding to tBDNF promoter II that corresponds with transcriptional repression. In contrast, enhanced binding of ten-eleven translocation protein 1 (Tet1), extracellular signal-regulated kinase 1/2 (ERK1/2), and cAMP response element-binding protein (CREB) to promoter III corresponds with transcriptional activation. These actions are accompanied by rapid modifications in histone methylation and phosphorylation status of RNA polymerase II (RNAP II). Significantly, these remarkably coordinated changes in epigenetic factors for two alternatively regulated tBDNF promoters during conditioning are controlled by Tet1 and ERK1/2. Our findings indicate that Tet1 and ERK1/2 are critical partners that, through complementary functions, control learning-dependent tBDNF promoter accessibility required for rapid transcription and acquisition of classical conditioning. FAU - Ambigapathy, Ganesh AU - Ambigapathy G AD - a Neuroscience Group; Basic Biomedical Sciences; University of South Dakota; Sanford School of Medicine ; Vermillion , SD USA. FAU - Zheng, Zhaoqing AU - Zheng Z AD - a Neuroscience Group; Basic Biomedical Sciences; University of South Dakota; Sanford School of Medicine ; Vermillion , SD USA. FAU - Keifer, Joyce AU - Keifer J AD - a Neuroscience Group; Basic Biomedical Sciences; University of South Dakota; Sanford School of Medicine ; Vermillion , SD USA. LA - eng GR - R01 NS051187/NS/NINDS NIH HHS/United States GR - NS051187/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Epigenetics JT - Epigenetics JID - 101265293 RN - 0 (Basic Helix-Loop-Helix Transcription Factors) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Chromatin) RN - 0 (DNA-Binding Proteins) RN - 0 (Methyl-CpG-Binding Protein 2) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) SB - IM MH - Animals MH - Basic Helix-Loop-Helix Transcription Factors/*genetics MH - Brain-Derived Neurotrophic Factor/*genetics MH - Chromatin/genetics MH - DNA Methylation/*genetics MH - DNA-Binding Proteins/genetics MH - *Learning MH - Methyl-CpG-Binding Protein 2 MH - Mitogen-Activated Protein Kinase 3/*genetics MH - Neurons/metabolism MH - Promoter Regions, Genetic MH - Turtles/genetics PMC - PMC5055205 OTO - NOTNLM OT - CREB OT - ChIP assays OT - Tet1 OT - classical conditioning OT - histones EDAT- 2015/09/05 06:00 MHDA- 2016/08/02 06:00 PMCR- 2016/09/04 CRDT- 2015/09/05 06:00 PHST- 2015/09/05 06:00 [entrez] PHST- 2015/09/05 06:00 [pubmed] PHST- 2016/08/02 06:00 [medline] PHST- 2016/09/04 00:00 [pmc-release] AID - 1090072 [pii] AID - 10.1080/15592294.2015.1090072 [doi] PST - ppublish SO - Epigenetics. 2015;10(10):981-93. doi: 10.1080/15592294.2015.1090072.