Activity-Induced Regulation of Synaptic Strength through the Chromatin Reader L3mbtl1
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Authors
Mao, WenjieSalzberg, Anna C.
Uchigashima, Motokazu
Hasegawa, Yuto
Hock, Hanno
Watanabe, Masahiko
Akbarian, Schahram
Kawasawa, Yuka Imamura.
Futai, Kensuke
Student Authors
Wenjie MaoAcademic Program
NeuroscienceUMass Chan Affiliations
Graduate School of Biomedical Sciences, Neuroscience ProgramFutai Lab
Neurobiology
Brudnick Neuropsychiatric Research Institute
Document Type
Journal ArticlePublication Date
2018-06-12Keywords
Neuroscience and Neurobiology
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Show full item recordAbstract
Homeostatic synaptic downscaling reduces neuronal excitability by modulating the number of postsynaptic receptors. Histone modifications and the subsequent chromatin remodeling play critical roles in activity-dependent gene expression. Histone modification codes are recognized by chromatin readers that affect gene expression by altering chromatin structure. We show that L3mbtl1 (lethal 3 malignant brain tumor-like 1), a polycomb chromatin reader, is downregulated by neuronal activity and is essential for synaptic response and downscaling. Genome-scale mapping of L3mbtl1 occupancies identified Ctnnb1 as a key gene downstream of L3mbtl1. Importantly, the occupancy of L3mbtl1 on the Ctnnb1 gene was regulated by neuronal activity. L3mbtl1 knockout neurons exhibited reduced Ctnnb1 expression. Partial knockdown of Ctnnb1 in wild-type neurons reduced excitatory synaptic transmission and abolished homeostatic downscaling, and transfecting Ctnnb1 in L3mbtl1 knockout neurons enhanced synaptic transmission and restored homeostatic downscaling. These results highlight a role for L3mbtl1 in regulating homeostasis of synaptic efficacy.Source
Cell Rep. 2018 Jun 12;23(11):3209-3222. doi: 10.1016/j.celrep.2018.05.028. Link to article on publisher's site
DOI
10.1016/j.celrep.2018.05.028Permanent Link to this Item
http://hdl.handle.net/20.500.14038/37952PubMed ID
29898393Related Resources
Rights
© 2018 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Distribution License
http://creativecommons.org/licenses/by-nc-nd/4.0/ae974a485f413a2113503eed53cd6c53
10.1016/j.celrep.2018.05.028
Scopus Count
Except where otherwise noted, this item's license is described as © 2018 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).