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Publication : NFIA co-localizes with PPARγ and transcriptionally controls the brown fat gene program.

First Author  Hiraike Y Year  2017
Journal  Nat Cell Biol Volume  19
Issue  9 Pages  1081-1092
PubMed ID  28812581 Mgi Jnum  J:247208
Mgi Id  MGI:5921913 Doi  10.1038/ncb3590
Citation  Hiraike Y, et al. (2017) NFIA co-localizes with PPARgamma and transcriptionally controls the brown fat gene program. Nat Cell Biol 19(9):1081-1092
abstractText  Brown fat dissipates energy as heat and protects against obesity. Here, we identified nuclear factor I-A (NFIA) as a transcriptional regulator of brown fat by a genome-wide open chromatin analysis of murine brown and white fat followed by motif analysis of brown-fat-specific open chromatin regions. NFIA and the master transcriptional regulator of adipogenesis, PPARgamma, co-localize at the brown-fat-specific enhancers. Moreover, the binding of NFIA precedes and facilitates the binding of PPARgamma, leading to increased chromatin accessibility and active transcription. Introduction of NFIA into myoblasts results in brown adipocyte differentiation. Conversely, the brown fat of NFIA-knockout mice displays impaired expression of the brown-fat-specific genes and reciprocal elevation of muscle genes. Finally, expression of NFIA and the brown-fat-specific genes is positively correlated in human brown fat. These results indicate that NFIA activates the cell-type-specific enhancers and facilitates the binding of PPARgamma to control the brown fat gene program.
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