Inhibition of KDM1A activity restores adult neurogenesis and improves hippocampal memory in a mouse model of Kabuki syndrome

Li Zhang; Genay Pilarowski; Emilio Merlo Pich; Atsushi Nakatani; John Dunlop; Rina Baba; Satoru Matsuda; Masaki Daini; Yasushi Hattori; Shigemitsu Matsumoto; Mitsuhiro Ito; Haruhide Kimura; Hans Tomas Bjornsson

doi:10.1016/j.omtm.2021.02.011

Inhibition of KDM1A activity restores adult neurogenesis and improves hippocampal memory in a mouse model of Kabuki syndrome

Li Zhang, Genay Pilarowski, Emilio Merlo Pich, Atsushi Nakatani, John Dunlop, Rina Baba, Satoru Matsuda, Masaki Daini, Yasushi Hattori, Shigemitsu Matsumoto, Mitsuhiro Ito, Haruhide Kimura, Hans Tomas Bjornsson

School of Medicine

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

KMT2D and KDM1A have opposing effects on histone 3 lysine 4 methylation. In this study, we show that TAK-418, an inhibitor of KDM1A, rescues abnormal gene expression and chromatin levels as well as defects of adult neurogenesis and hippocampal memory in a mouse model of Kabuki syndrome carrying a mutation in Kmt2d.

Original language	English (US)
Pages (from-to)	779-791
Number of pages	13
Journal	Molecular Therapy - Methods and Clinical Development
Volume	20
DOIs	https://doi.org/10.1016/j.omtm.2021.02.011
State	Published - Mar 12 2021

Keywords

ERK
H3K4me1
H3K4me3
LSD1
adult neurogenesis
chromatin
epigenetics
histone modification
splenomegaly
therapeutics

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology
Genetics

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Zhang, L., Pilarowski, G., Pich, E. M., Nakatani, A., Dunlop, J., Baba, R., Matsuda, S., Daini, M., Hattori, Y., Matsumoto, S., Ito, M., Kimura, H., & Bjornsson, H. T. (2021). Inhibition of KDM1A activity restores adult neurogenesis and improves hippocampal memory in a mouse model of Kabuki syndrome. Molecular Therapy - Methods and Clinical Development, 20, 779-791. https://doi.org/10.1016/j.omtm.2021.02.011

Zhang, L, Pilarowski, G, Pich, EM, Nakatani, A, Dunlop, J, Baba, R, Matsuda, S, Daini, M, Hattori, Y, Matsumoto, S, Ito, M, Kimura, H & Bjornsson, HT 2021, 'Inhibition of KDM1A activity restores adult neurogenesis and improves hippocampal memory in a mouse model of Kabuki syndrome', Molecular Therapy - Methods and Clinical Development, vol. 20, pp. 779-791. https://doi.org/10.1016/j.omtm.2021.02.011

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abstract = "KMT2D and KDM1A have opposing effects on histone 3 lysine 4 methylation. In this study, we show that TAK-418, an inhibitor of KDM1A, rescues abnormal gene expression and chromatin levels as well as defects of adult neurogenesis and hippocampal memory in a mouse model of Kabuki syndrome carrying a mutation in Kmt2d.",

keywords = "ERK, H3K4me1, H3K4me3, LSD1, adult neurogenesis, chromatin, epigenetics, histone modification, splenomegaly, therapeutics",

author = "Li Zhang and Genay Pilarowski and Pich, {Emilio Merlo} and Atsushi Nakatani and John Dunlop and Rina Baba and Satoru Matsuda and Masaki Daini and Yasushi Hattori and Shigemitsu Matsumoto and Mitsuhiro Ito and Haruhide Kimura and Bjornsson, {Hans Tomas}",

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doi = "10.1016/j.omtm.2021.02.011",

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T1 - Inhibition of KDM1A activity restores adult neurogenesis and improves hippocampal memory in a mouse model of Kabuki syndrome

AU - Zhang, Li

AU - Pilarowski, Genay

AU - Pich, Emilio Merlo

AU - Nakatani, Atsushi

AU - Dunlop, John

AU - Baba, Rina

AU - Matsuda, Satoru

AU - Daini, Masaki

AU - Hattori, Yasushi

AU - Matsumoto, Shigemitsu

AU - Ito, Mitsuhiro

AU - Kimura, Haruhide

AU - Bjornsson, Hans Tomas

PY - 2021/3/12

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AB - KMT2D and KDM1A have opposing effects on histone 3 lysine 4 methylation. In this study, we show that TAK-418, an inhibitor of KDM1A, rescues abnormal gene expression and chromatin levels as well as defects of adult neurogenesis and hippocampal memory in a mouse model of Kabuki syndrome carrying a mutation in Kmt2d.

KW - ERK

KW - H3K4me1

KW - H3K4me3

KW - LSD1

KW - adult neurogenesis

KW - chromatin

KW - epigenetics

KW - histone modification

KW - splenomegaly

KW - therapeutics

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ER -

Inhibition of KDM1A activity restores adult neurogenesis and improves hippocampal memory in a mouse model of Kabuki syndrome

Abstract

Keywords

ASJC Scopus subject areas

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