例如:"lncRNA", "apoptosis", "WRKY"

Glucocorticoid Receptor Accelerates, but Is Dispensable for, Adipogenesis.

Mol. Cell. Biol.2017 Jan 04;37(2)
Young-Kwon Park 1 , Kai Ge 2
Young-Kwon Park 1 , Kai Ge 2

[No authors listed]

Author information
  • 1 Adipocyte Biology and Gene Regulation Section, LERB, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • 2 Adipocyte Biology and Gene Regulation Section, LERB, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA kai.ge@nih.gov.

摘要


Dexamethasone (DEX), a synthetic ligand for glucocorticoid receptor (GR), is routinely used to stimulate adipogenesis in culture. GR-depleted preadipocytes show adipogenesis defects 1 week after induction of differentiation. However, it has remained unclear whether GR is required for adipogenesis in vivo By deleting GR in precursors of brown adipocytes, we found unexpectedly that GR is dispensable for brown adipose tissue development in mice. In culture, GR-deficient primary or immortalized white and brown preadipocytes showed severely delayed adipogenesis 1 week after induction of differentiation. However, when differentiation was extended to 3 weeks, GR-deficient preadipocytes showed levels of adipogenesis marker expression and lipid accumulation similar to those of the wild-type cells, indicating that DEX-bound GR accelerates, but is dispensable for, adipogenesis. Consistently, DEX accelerates, but is dispensable for, adipogenesis in culture. We show that DEX-bound GR accelerates adipogenesis by directly promoting the expression of adipogenic transcription factors CCAAT/enhancer-binding protein alpha (C/EBPα), C/EBPβ, C/EBPδ, KLF5, KLF9, and peroxisome proliferator-activated receptor γ (PPARγ) in the early phase of differentiation. Mechanistically, DEX-bound GR recruits histone H3K27 acetyltransferase CBP to promote activation of C/EBPβ-primed enhancers of adipogenic genes. These results clarify the role of GR in adipogenesis in vivo and demonstrate that DEX-mediated activation of GR accelerates, but is dispensable for, adipogenesis.

KEYWORDS: GR, adipogenesis, dexamethasone, glucocorticoid receptor

原始数据


 保存测序数据
Sample name
Organism Experiment title Sample type Library instrument Attributes
cell typechip antibodychip antibody vendorsource namestage of adipogenesisstrain
RNA_cre_4h
Mus musculus GSM2029201: RNA_cre_4h; Mus musculus; RNA-Seq RNA-Seq Illumina HiSeq 2500 immortalized GR-flox/flox brown preadipocytes Brown preadipocyte cell 4h C57BL/6J
RNA_vec_4h
Mus musculus GSM2029200: RNA_vec_4h; Mus musculus; RNA-Seq RNA-Seq Illumina HiSeq 2500 immortalized GR-flox/flox brown preadipocytes Brown preadipocyte cell 4h C57BL/6J
RNA_cre_D7
Mus musculus GSM2029199: RNA_cre_D7; Mus musculus; RNA-Seq RNA-Seq Illumina HiSeq 2500 immortalized GR-flox/flox brown preadipocytes Brown preadipocyte cell day 7 C57BL/6J
RNA_vec_D7
Mus musculus GSM2029198: RNA_vec_D7; Mus musculus; RNA-Seq RNA-Seq Illumina HiSeq 2500 immortalized GR-flox/flox brown preadipocytes Brown preadipocyte cell day 7 C57BL/6J
RNA_cre_D2
Mus musculus GSM2029197: RNA_cre_D2; Mus musculus; RNA-Seq RNA-Seq Illumina HiSeq 2500 immortalized GR-flox/flox brown preadipocytes Brown preadipocyte cell day 2 C57BL/6J