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| Status |
Public on Nov 01, 2016 |
| Title |
GR accelerates, but is largely dispensable for, adipogenesis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Dexamethasone (DEX), a synthetic ligand for glucocorticoid receptor (GR), is routinely used to stimulate adipogenesis in culture. GR-depleted preadipocytes show adipogenesis defects one 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 one week after induction of differentiation. However, when differentiation was extended to 3 weeks, GR-deficient preadipocytes showed similar levels of adipogenesis marker expression and lipid accumulation as 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 C/EBPb, C/EBPd, C/EBPa, KLF5, KLF9 and PPARg in the early phase of differentiation. Mechanistically, DEX-bound GR recruits histone H3K27 acetyltransferase CBP to promote activation of C/EBPb-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.
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| Overall design |
Expression profiling by RNA-seq at four time points (D0, 4h, D2, D7). Profiling of transcription factors (GR, C/EBPβ, p-CREB) binding, co-factors (CBP) binding and histone modifications (H3K4me1, H3K27ac) by ChIP-seq at two time points (0h, 4h) during adipogenesis of GRf/f brown preadipocytes in culture.
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| Contributor(s) |
Park Y, Ge K |
| Citation(s) |
27777311 |
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| Submission date |
Jan 07, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Kai Ge |
| E-mail(s) |
kai.ge@nih.gov
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| Phone |
301-451-1998
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| Organization name |
NIH
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| Department |
NIDDK
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| Street address |
50 South Dr Rm 4154
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (30)
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| Relations |
| BioProject |
PRJNA308178 |
| SRA |
SRP068185 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE76619_RAW.tar |
264.6 Mb |
(http)(custom) |
TAR (of TXT, WIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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