Kyushu University [Katayama Yuta (Assistant Professor) Medical Institute of Bioregulation, Department of Molecular and Cellular Biology]

Katayama Yuta

Last modified date：2019.06.27

Assistant Professor / Department of Molecular and Cellular Biology
Medical Institute of Bioregulation

1 Research Interests

2 Academic Activities

2.1 Papers

3 Membership in Academic Society

E-Mail

Homepage

http://www.bioreg.kyushu-u.ac.jp/saibou/index.html

Phone

092-942-6820

Fax

092-642-6819

Academic Degree

Ph.D

Country of degree conferring institution (Overseas)

Field of Specialization

Molecular biology

Research

Research Interests

Molecular pathogenesis of ASD with abnormal chromatin remodeling
keyword : Chromatin, CHD8, ASD
2018.04.

Academic Activities

Papers

Show All Papers >>

Yuta Katayama, Masaaki Nishiyama, Hirotaka Shoji, Yasuyuki Ohkawa, Atsuki Kawamura, Tetsuya Sato, Mikita Suyama, Toru Takumi, Tsuyoshi Miyakawa, Keiichi Nakayama, CHD8 haploinsufficiency results in autistic-like phenotypes in mice, Nature, 10.1038/nature19357, 537, 7622, 675-679, 2016.01, Autism spectrum disorder (ASD) comprises a range of neurodevelopmental disorders characterized by deficits in social interaction and communication as well as by restricted and repetitive behaviours. ASD has a strong genetic component with high heritability. Exome sequencing analysis has recently identified many de novo mutations in a variety of genes in individuals with ASD, with CHD8, a gene encoding a chromatin remodeller, being most frequently affected. Whether CHD8 mutations are causative for ASD and how they might establish ASD traits have remained unknown. Here we show that mice heterozygous for Chd8 mutations manifest ASD-like behavioural characteristics including increased anxiety, repetitive behaviour, and altered social behaviour. CHD8 haploinsufficiency did not result in prominent changes in the expression of a few specific genes but instead gave rise to small but global changes in gene expression in the mouse brain, reminiscent of those in the brains of patients with ASD. Gene set enrichment analysis revealed that neurodevelopment was delayed in the mutant mouse embryos. Furthermore, reduced expression of CHD8 was associated with abnormal activation of RE-1 silencing transcription factor (REST), which suppresses the transcription of many neuronal genes. REST activation was also observed in the brains of humans with ASD, and CHD8 was found to interact physically with REST in the mouse brain. Our results are thus consistent with the notion that CHD8 haploinsufficiency is a highly penetrant risk factor for ASD, with disease pathogenesis probably resulting from a delay in neurodevelopment..

Membership in Academic Society

The Molecular Biology Society of Japan

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