TY - JOUR
T1 - The Autism-Related Protein CHD8 Cooperates with C/EBPβ to Regulate Adipogenesis
AU - Kita, Yasuyuki
AU - Katayama, Yuta
AU - Shiraishi, Taichi
AU - Oka, Takeru
AU - Sato, Tetsuya
AU - Suyama, Mikita
AU - Ohkawa, Yasuyuki
AU - Miyata, Keishi
AU - Oike, Yuichi
AU - Shirane, Michiko
AU - Nishiyama, Masaaki
AU - Nakayama, Keiichi I.
N1 - Funding Information:
We thank T. Kitamura and T. Akagi for providing vectors and DNA; N. Nishimura, K. Tsunematsu, and other laboratory members for technical assistance; and A. Ohta for help in preparation of the manuscript. This study was funded in part by KAKENHI grants (2522130, 26640080, and 17H06301) from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan . It was also supported in part by a Japan Society for the Promotion of Science (JSPS) fellowship ( 13J04520 ) to Y. Kita.
Publisher Copyright:
© 2018 The Author(s)
PY - 2018/5/15
Y1 - 2018/5/15
N2 - 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.
AB - 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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U2 - 10.1016/j.celrep.2018.04.050
DO - 10.1016/j.celrep.2018.04.050
M3 - Article
C2 - 29768199
AN - SCOPUS:85046625103
SN - 2211-1247
VL - 23
SP - 1988
EP - 2000
JO - Cell Reports
JF - Cell Reports
IS - 7
ER -