Brudnick Neuropsychiatric Research Institute; Department of Neurobiology; Futai Lab; Graduate School of Biomedical Sciences, Program in Neuroscience
Neuroscience and Neurobiology
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.
Rights and Permissions
© 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/).
DOI of Published Version
Cell Rep. 2018 Jun 12;23(11):3209-3222. doi: 10.1016/j.celrep.2018.05.028. Link to article on publisher's site
Mao, Wenjie; Salzberg, Anna C.; Uchigashima, Motokazu; Hasegawa, Yuto; Hock, Hanno; Watanabe, Masahiko; Akbarian, Schahram; Kawasawa, Yuka Imamura.; and Futai, Kensuke, "Activity-Induced Regulation of Synaptic Strength through the Chromatin Reader L3mbtl1" (2018). Neurobiology Publications and Presentations. 225.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.