Histone Methylation by the Kleefstra Syndrome Protein EHMT1 Mediates Homeostatic Synaptic Scaling
| العنوان: | Histone Methylation by the Kleefstra Syndrome Protein EHMT1 Mediates Homeostatic Synaptic Scaling |
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| المؤلفون: | Jason M. Keller, Martijn Selten, Giovanni Iacono, Hans van Bokhoven, Roberta Mancini, Astrid R. Oudakker, Monica Frega, Wei Ba, Henk Stunnenberg, Tjitske Kleefstra, Nael Nadif Kasri, Huiqing Zhou, Marco Benevento, Elly Lewerissa |
| المصدر: | Neuron, 91, 2, pp. 341-355 Neuron, 91, 341-355 |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | 0301 basic medicine, Heart Defects, Congenital, Patch-Clamp Techniques, Nonsynaptic plasticity, Mice, Transgenic, Biology, Hippocampus, Methylation, Craniofacial Abnormalities, Histones, 03 medical and health sciences, Homeostatic plasticity, Intellectual Disability, Neuroplasticity, Metaplasticity, Histone methylation, Animals, Homeostasis, Molecular Biology, Synaptic scaling, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Neuronal Plasticity, General Neuroscience, Brain-Derived Neurotrophic Factor, Histone-Lysine N-Methyltransferase, 030104 developmental biology, Synaptic fatigue, Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10], Synaptic plasticity, Synapses, Molecular Developmental Biology, Chromosome Deletion, Chromosomes, Human, Pair 9, Neuroscience |
| الوصف: | Contains fulltext : 166300.pdf (Publisher’s version ) (Open Access) Homeostatic plasticity, a form of synaptic plasticity, maintains the fine balance between overall excitation and inhibition in developing and mature neuronal networks. Although the synaptic mechanisms of homeostatic plasticity are well characterized, the associated transcriptional program remains poorly understood. We show that the Kleefstra-syndrome-associated protein EHMT1 plays a critical and cell-autonomous role in synaptic scaling by responding to attenuated neuronal firing or sensory drive. Chronic activity deprivation increased the amount of neuronal dimethylated H3 at lysine 9 (H3K9me2), the catalytic product of EHMT1 and an epigenetic marker for gene repression. Genetic knockdown and pharmacological blockade of EHMT1 or EHMT2 prevented the increase of H3K9me2 and synaptic scaling up. Furthermore, BDNF repression was preceded by EHMT1/2-mediated H3K9me2 deposition at the Bdnf promoter during synaptic scaling up, both in vitro and in vivo. Our findings suggest that H3K9me2-mediated changes in chromatin structure govern a repressive program that controls synaptic scaling. 15 p. |
| وصف الملف: | application/pdf |
| تدمد: | 1097-4199 0896-6273 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4d354d52b80ffaf92c9339fd2bc4e777 https://pubmed.ncbi.nlm.nih.gov/27373831 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4d354d52b80ffaf92c9339fd2bc4e777 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10974199 08966273 |
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