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| Status |
Public on Sep 22, 2020 |
| Title |
NFIA differentially controls adipogenic and myogenic gene program through distinct pathways to ensure adipocyte differentiation [chromatin] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The transcription factor nuclear factor I-A (NFIA) is a regulator of brown adipocyte differentiation. Here we show that the C-terminal 17 amino acid residues of NFIA (which we named pro#3 domain) is required for transcriptional activity of NFIA. Full-length NFIA, but not deletion mutant lacking pro#3 domain rescued impaired Pparg expression and adipogenesis in NFIA-knockout cells. Mechanistically, the ability of NFIA to increase chromatin accessibility is mediated through pro#3 domain. However, the deletion mutant still binds to Myod1 enhancer to decrease chromatin accessibility and represses Myod1 as well as proximally transcribed non-coding RNA called DRReRNA, leading to suppression of myogenic gene program. Therefore, the negative effect of NFIA on myogenic gene program is, at least in part, independent from the positive effect on Pparg expression and its downstream adipogenic gene program. These results uncover multiple ways of action of NFIA to ensure optimal regulation of brown adipocyte differentiation.
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| Overall design |
ChIP-seq , FAIRE-seq and RNA-seq analysis of control-, full-length NFIA and Δpro#3 mutant-expressing C2C12 myoblasts and RNA-seq analysis of NFIA-KO ingSVF cells
ChIP target is Flag-tagged wildtype or delta pro#3 mutant NFIA.
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| Contributor(s) |
Hiraike Y, Waki H, Oguchi M, Tsutsumi S, Aburatani H, Yamauchi T, Kadowaki T |
| Citation(s) |
32991581 |
| |
| Submission date |
Apr 26, 2019 |
| Last update date |
Dec 22, 2020 |
| Contact name |
Hironori Waki |
| E-mail(s) |
[email protected]
|
| Organization name |
The University of Tokyo
|
| Street address |
Hongo 7-3-1, Bunkyo-ku
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| City |
Tokyo |
| ZIP/Postal code |
1138655 |
| Country |
Japan |
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| Platforms (2) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
| GPL16417 |
Illumina MiSeq (Mus musculus) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE130390 |
NFIA differentially controls adipogenic and myogenic gene program through distinct pathways to ensure adipocyte differentiation |
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| Relations |
| BioProject |
PRJNA539969 |
| SRA |
SRP193994 |
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