Activity-Induced Regulation of Synaptic Strength through the Chromatin Reader L3mbtl1

Wenjie Mao, Anna C. Salzberg, Motokazu Uchigashima, Yuto Hasegawa, Hanno Hock, Masahiko Watanabe, Schahram Akbarian, Yuka Imamura Kawasawa, Kensuke Futai

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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. Synaptic homeostasis is crucial for maintaining proper neuronal excitability and excitatory/inhibitory balance in the brain. Mao et al. report that an activity-dependent chromatin reader protein is required for homeostatic control of synaptic strength through the regulation of downstream target gene Ctnnb1.

Original languageEnglish (US)
Pages (from-to)3209-3222
Number of pages14
JournalCell Reports
Volume23
Issue number11
DOIs
StatePublished - Jun 12 2018

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Brain Neoplasms
Chromatin
Tumors
Brain
Histone Code
Genes
Neurons
Synaptic Transmission
Gene expression
Histones
Homeostasis
Lethal Genes
Gene Expression
Chromatin Assembly and Disassembly
Chromosome Mapping
Down-Regulation
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Mao, W., Salzberg, A. C., Uchigashima, M., Hasegawa, Y., Hock, H., Watanabe, M., ... Futai, K. (2018). Activity-Induced Regulation of Synaptic Strength through the Chromatin Reader L3mbtl1. Cell Reports, 23(11), 3209-3222. https://doi.org/10.1016/j.celrep.2018.05.028
Mao, Wenjie ; Salzberg, Anna C. ; Uchigashima, Motokazu ; Hasegawa, Yuto ; Hock, Hanno ; Watanabe, Masahiko ; Akbarian, Schahram ; Kawasawa, Yuka Imamura ; Futai, Kensuke. / Activity-Induced Regulation of Synaptic Strength through the Chromatin Reader L3mbtl1. In: Cell Reports. 2018 ; Vol. 23, No. 11. pp. 3209-3222.
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Mao, W, Salzberg, AC, Uchigashima, M, Hasegawa, Y, Hock, H, Watanabe, M, Akbarian, S, Kawasawa, YI & Futai, K 2018, 'Activity-Induced Regulation of Synaptic Strength through the Chromatin Reader L3mbtl1', Cell Reports, vol. 23, no. 11, pp. 3209-3222. https://doi.org/10.1016/j.celrep.2018.05.028

Activity-Induced Regulation of Synaptic Strength through the Chromatin Reader L3mbtl1. / Mao, Wenjie; Salzberg, Anna C.; Uchigashima, Motokazu; Hasegawa, Yuto; Hock, Hanno; Watanabe, Masahiko; Akbarian, Schahram; Kawasawa, Yuka Imamura; Futai, Kensuke.

In: Cell Reports, Vol. 23, No. 11, 12.06.2018, p. 3209-3222.

Research output: Contribution to journalArticle

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AU - Mao, Wenjie

AU - Salzberg, Anna C.

AU - Uchigashima, Motokazu

AU - Hasegawa, Yuto

AU - Hock, Hanno

AU - Watanabe, Masahiko

AU - Akbarian, Schahram

AU - Kawasawa, Yuka Imamura

AU - Futai, Kensuke

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Mao W, Salzberg AC, Uchigashima M, Hasegawa Y, Hock H, Watanabe M et al. Activity-Induced Regulation of Synaptic Strength through the Chromatin Reader L3mbtl1. Cell Reports. 2018 Jun 12;23(11):3209-3222. https://doi.org/10.1016/j.celrep.2018.05.028