title: Inhibition of G9a/GLP Complex Promotes Long-Term Potentiation and Synaptic Tagging/Capture in Hippocampal CA1 Pyramidal Neurons.
abstract: Epigenetic regulations play an important role in regulating the learning and memory processes. G9a/G9a-like protein (GLP) lysine dimethyltransferase complex controls a prominent histone H3 lysine9 dimethylation (H3K9me2) that results in transcriptional silencing of the chromatin. Here, we report that the inhibition of G9a/GLP complex by either of the substrate competitive inhibitors UNC 0638 or BIX 01294 reinforces protein synthesis-independent long-term potentiation (early-LTP) to protein synthesis-dependent long-term potentiation (late-LTP). The reinforcement effect was observed if the inhibitors were present during the induction of early-LTP and in addition when G9a/GLP complex inhibition was carried out by priming of synapses within an interval of 30 min before or after the induction of early-LTP. Surprisingly, the reinforced LTP by G9a/GLP complex inhibition was able to associate with a weak plasticity event from nearby independent synaptic populations, resulting in synaptic tagging/capture (STC). We have identified brain-derived neurotrophic factor (BDNF) as a critical plasticity protein that maintains G9a/GLP complex inhibition-mediated LTP facilitation and its STC. Our study reveals an epigenetic mechanism for promoting plasticity and associativity by G9a/GLP complex inhibition, and it may engender a promising epigenetic target for enhancing memory in neural networks.
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117 597, Singapore.|Neurobiology/Aging Program, #04-44, 28 Medical Drive, Life Sciences Institute (LSI), National University of Singapore, Singapore 117 456, Singapore.
authors.forename: Mahima
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117 597, Singapore.|Neurobiology/Aging Program, #04-44, 28 Medical Drive, Life Sciences Institute (LSI), National University of Singapore, Singapore 117 456, Singapore.
authors.forename: Nuralyah Bte
authors.initials: NB
authors.lastname: Razali
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117 597, Singapore.|Neurobiology/Aging Program, #04-44, 28 Medical Drive, Life Sciences Institute (LSI), National University of Singapore, Singapore 117 456, Singapore.
authors.forename: Sreedharan
authors.initials: S
authors.lastname: Sajikumar
mesh_terms: D000818:Animals; D001381:Azepines / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D056547:CA1 Region, Hippocampal / Q000166:cytology*; D047369:Chromatin Immunoprecipitation; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008954:Models, Biological; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D011799:Quinazolines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
chemical_list: D001381:Azepines; C518299:BIX 01294; D019208:Brain-Derived Neurotrophic Factor; D004791:Enzyme Inhibitors; D011799:Quinazolines; C561310:UNC 0638; C577330:Ehmt2 protein, rat; D011495:Histone-Lysine N-Methyltransferase
keywords: BDNF; G9a/GLP; long-term potentiation; metaplasticity; synaptic tagging; synaptic tagging and capture