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。

棕色脂肪以热量的形式散发能量并防止肥胖。在这里，我们通过对小鼠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，将核因子 IA (NFIA) 鉴定为棕色脂肪的转录调节因子。NFIA 和脂肪生成的主要转录调节因子 PPARγ 共同定位于棕色脂肪特异性增强子。此外，NFIA 的结合先于并促进 PPARγ 的结合，导致染色质可及性和活性转录增加。将 NFIA 引入成肌细胞会导致棕色脂肪细胞分化。相反，NFIA 基因敲除小鼠的棕色脂肪表现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，NFIA 和棕色脂肪特异性基因的表达在人类棕色脂肪中呈正相关。这些结果表明 NFIA 激活细胞类型特异性增强子并促进 PPARγ 的结合以控制棕色脂肪基因程序。