1. The Autism-Related Protein CHD8 Cooperates with C/EBPβ to Regulate Adipogenesis
- Author
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Mikita Suyama, Keishi Miyata, Yasuyuki Ohkawa, Keiichi I. Nakayama, Yasuyuki Kita, Tetsuya Sato, Taichi Shiraishi, Michiko Shirane, Takeru Oka, Masaaki Nishiyama, Yuichi Oike, and Yuta Katayama
- Subjects
0301 basic medicine ,Adipose Tissue, White ,White adipose tissue ,Biology ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Transactivation ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Downregulation and upregulation ,Adipocyte ,3T3-L1 Cells ,Adipocytes ,CCAAT-Enhancer-Binding Protein-alpha ,Animals ,Humans ,Autistic Disorder ,Receptor ,Adipogenesis ,Genome ,CCAAT-Enhancer-Binding Protein-beta ,Hypertrophy ,Chromatin ,Cell biology ,DNA-Binding Proteins ,Mice, Inbred C57BL ,PPAR gamma ,030104 developmental biology ,HEK293 Cells ,chemistry ,Gene Expression Regulation ,Haploinsufficiency ,030217 neurology & neurosurgery ,Protein Binding - 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.
- Published
- 2017