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, PPARγ, co-localize at the brown-fat-specific enhancers. Moreover, the binding of NFIA precedes and facilitates the binding of PPARγ, 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 PPARγ to control the brown fat gene program.

中文翻译：

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NFIA与PPARγ共定位并转录控制棕色脂肪基因程序

棕色脂肪通过热量散发能量并防止肥胖。在这里，我们通过对鼠科动物棕色和白色脂肪进行全基因组开放染色质分析，然后对棕色脂肪特异性开放染色质区域进行基序分析，确定了核因子IA（NFIA）是棕色脂肪的转录调节因子。NFIA和脂肪生成，PPAR的主转录调节γ在褐色脂肪特异性增强子，共定位。此外，NFIA先于的结合并促进PPAR的结合γ，导致染色质可及性增加和活跃的转录。将NFIA引入成肌细胞会导致褐色脂肪细胞分化。相反，敲除NFIA的小鼠的棕色脂肪显示出棕色脂肪特异性基因的表达受损和肌肉基因的相互升高。最后，在人的棕色脂肪中，NFIA和棕色脂肪特异性基因的表达呈正相关。这些结果表明，NFIA激活细胞类型特异性增强子和促进PPAR结合γ来控制棕色脂肪基因程序。