The Autism-Related Protein CHD8 Cooperates with C/EBPβ to Regulate Adipogenesis

Yasuyuki Kita, Yuta Katayama, Taichi Shiraishi, Takeru Oka, Tetsuya Sato, Mikita Suyama, Yasuyuki Ohkawa, Keishi Miyata, Yuichi Oike, Michiko Shirane, Masaaki Nishiyama, Keiichi I. Nakayama

研究成果: ジャーナルへの寄稿記事

抄録

The gene encoding the chromatin remodeler CHD8 is the most frequently mutated gene in individuals with autism spectrum disorder (ASD). Heterozygous mutations in CHD8 give rise to ASD that is often accompanied by macrocephaly, gastrointestinal complaints, and slender habitus. Whereas most phenotypes of CHD8 haploinsufficiency likely result from delayed neurodevelopment, the mechanism underlying slender habitus has remained unknown. Here, we show that CHD8 interacts with CCAAT/enhancer-binding protein β (C/EBPβ) and promotes its transactivation activity during adipocyte differentiation. Adipogenesis was impaired in Chd8-deleted preadipocytes, with the upregulation of C/EBPα and peroxisome-proliferator-activated receptor γ (PPARγ), two master regulators of this process, being attenuated in mutant cells. Furthermore, mice with CHD8 ablation in white preadipocytes had a markedly reduced white adipose tissue mass. Our findings reveal a mode of C/EBPβ regulation by CHD8 during adipogenesis, with CHD8 deficiency resulting in a defect in the development of white adipose tissue. Kita et al. show that autism-related protein CHD8 is essential for adipogenesis and the development of white adipose tissue. Moreover, they demonstrate that CHD8 cooperates with C/EBPβ to regulate transactivation of the genes for C/EBPα and PPARγ during adipogenesis.

元の言語英語
ページ(範囲)1988-2000
ページ数13
ジャーナルCell Reports
23
発行部数7
DOI
出版物ステータス出版済み - 5 15 2018

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CCAAT-Enhancer-Binding Proteins
Adipogenesis
Autistic Disorder
White Adipose Tissue
Peroxisome Proliferator-Activated Receptors
Tissue
Proteins
Transcriptional Activation
Genes
Megalencephaly
Haploinsufficiency
Gene encoding
Ablation
Adipocytes
Chromatin
Up-Regulation
Phenotype
Defects
Mutation

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

これを引用

The Autism-Related Protein CHD8 Cooperates with C/EBPβ to Regulate Adipogenesis. / Kita, Yasuyuki; Katayama, Yuta; Shiraishi, Taichi; Oka, Takeru; Sato, Tetsuya; Suyama, Mikita; Ohkawa, Yasuyuki; Miyata, Keishi; Oike, Yuichi; Shirane, Michiko; Nishiyama, Masaaki; Nakayama, Keiichi I.

:: Cell Reports, 巻 23, 番号 7, 15.05.2018, p. 1988-2000.

研究成果: ジャーナルへの寄稿記事

Kita, Y, Katayama, Y, Shiraishi, T, Oka, T, Sato, T, Suyama, M, Ohkawa, Y, Miyata, K, Oike, Y, Shirane, M, Nishiyama, M & Nakayama, KI 2018, 'The Autism-Related Protein CHD8 Cooperates with C/EBPβ to Regulate Adipogenesis', Cell Reports, 巻. 23, 番号 7, pp. 1988-2000. https://doi.org/10.1016/j.celrep.2018.04.050
Kita, Yasuyuki ; Katayama, Yuta ; Shiraishi, Taichi ; Oka, Takeru ; Sato, Tetsuya ; Suyama, Mikita ; Ohkawa, Yasuyuki ; Miyata, Keishi ; Oike, Yuichi ; Shirane, Michiko ; Nishiyama, Masaaki ; Nakayama, Keiichi I. / The Autism-Related Protein CHD8 Cooperates with C/EBPβ to Regulate Adipogenesis. :: Cell Reports. 2018 ; 巻 23, 番号 7. pp. 1988-2000.
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abstract = "The gene encoding the chromatin remodeler CHD8 is the most frequently mutated gene in individuals with autism spectrum disorder (ASD). Heterozygous mutations in CHD8 give rise to ASD that is often accompanied by macrocephaly, gastrointestinal complaints, and slender habitus. Whereas most phenotypes of CHD8 haploinsufficiency likely result from delayed neurodevelopment, the mechanism underlying slender habitus has remained unknown. Here, we show that CHD8 interacts with CCAAT/enhancer-binding protein β (C/EBPβ) and promotes its transactivation activity during adipocyte differentiation. Adipogenesis was impaired in Chd8-deleted preadipocytes, with the upregulation of C/EBPα and peroxisome-proliferator-activated receptor γ (PPARγ), two master regulators of this process, being attenuated in mutant cells. Furthermore, mice with CHD8 ablation in white preadipocytes had a markedly reduced white adipose tissue mass. Our findings reveal a mode of C/EBPβ regulation by CHD8 during adipogenesis, with CHD8 deficiency resulting in a defect in the development of white adipose tissue. Kita et al. show that autism-related protein CHD8 is essential for adipogenesis and the development of white adipose tissue. Moreover, they demonstrate that CHD8 cooperates with C/EBPβ to regulate transactivation of the genes for C/EBPα and PPARγ during adipogenesis.",
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