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

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1988-2000
Number of pages13
JournalCell Reports
Volume23
Issue number7
DOIs
Publication statusPublished - May 15 2018

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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