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Dynamic chromatin remodeling events in hippocampal neurons are associated with NMDA receptor‐mediated activation of Bdnf gene promoter 1
Author(s) -
Tian Feng,
Hu XianZhang,
Wu Xuan,
Jiang Hong,
Pan Hongna,
Marini Ann M.,
Lipsky Robert H.
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06058.x
Subject(s) - chromatin immunoprecipitation , creb , histone h3 , biology , nmda receptor , promoter , microbiology and biotechnology , rna polymerase ii , brain derived neurotrophic factor , chromatin remodeling , histone , transcription factor , neurotrophic factors , receptor , gene expression , genetics , gene
To determine the epigenetic events associated with NMDA receptor‐mediated activation of brain‐derived neurotrophic factor gene ( Bdnf ) promoter 1 by hippocampal neurons in culture, we screened 12 loci across 4.5 kb of genomic DNA 5′ of the transcription start site (TSS) of rat Bdnf for specific changes in histone modification and transcription factor binding following NMDA receptor stimulation. Chromatin immunoprecipitation (ChIP) assays showed that NMDA receptor stimulation produced a durable, time‐dependent decrease in histone H3 at lysine 9 dimethylation (H3K9me2), within 3 h after NMDA treatment across multiple loci. Concomitant increases in H3K4me2 and H3K9/14 acetylation (H3AcK9/14) were associated with transcriptional activation, but occurred at fewer sites within the promoter. The decrease in H3K9me2 was associated with release of HDAC1, MBD1, MeCP2, and REST from specific locations within promoter 1, although with different kinetics. In addition, occupancy of sites proximal to and distal to the TSS by the transcription factors NF‐κB, CREB‐binding protein (CBP), and cAMP‐response element‐binding protein were correlated with increased occupancy of RNA polymerase II at two loci proximal to the TSS following NMDA receptor stimulation. These temporal changes in promoter occupancy could occur thousands of base pairs 5′ of the TSS, suggesting a mechanism that produces waves of Bdnf transcription.