MED1 often serves as a surrogate of the general transcription coactivator complex Mediator for identifying active enhancers. MED1 is required for phenotypic conversion of fibroblasts to adipocytes in vitro, but its role in adipose development and expansion in vivo has not been reported. Here, we show that MED1 is not generally required for transcription during adipogenesis in culture and that MED1 is dispensable for adipose development in mice. Instead, MED1 is required for postnatal adipose expansion and the induction of fatty acid and triglyceride synthesis genes after pups switch diet from high-fat maternal milk to carbohydrate-based chow. During adipogenesis, MED1 is dispensable for induction of lineage-determining transcription factors (TFs) PPARγ and C/EBPα but is required for lipid accumulation in the late phase of differentiation. Mechanistically, MED1 controls the induction of lipogenesis genes by facilitating lipogenic TF ChREBP- and SREBP1a-dependent recruitment of Mediator to active enhancers. Together, our findings identify a cell- and gene-specific regulatory role of MED1 as a lipogenesis coactivator required for postnatal adipose expansion.

中文翻译：

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MED1 是产后脂肪扩张所需的脂肪生成共激活剂

MED1 通常作为通用转录辅激活因子复合体 Mediator 的替代物，用于识别活性增强子。MED1 是体外成纤维细胞表型转化为脂肪细胞所必需的，但尚未报道其在体内脂肪发育和扩张中的作用。在这里，我们表明 MED1 在培养的脂肪形成过程中通常不需要转录，并且 MED1 对于小鼠的脂肪发育是可有可无的。相反，在幼崽将饮食从高脂母奶转向以碳水化合物为基础的食物后，MED1 是出生后脂肪扩张和脂肪酸和甘油三酯合成基因诱导所必需的。在脂肪生成过程中，MED1 对于谱系决定转录因子 (TFs) PPARγ 和 C/EBPα 的诱导是可有可无的，但在分化后期脂质积累是必需的。从机制上讲，MED1 通过促进脂肪生成 TF ChREBP 和 SREBP1a 依赖性介质向活性增强剂的募集来控制脂肪生成基因的诱导。总之，我们的发现确定了 MED1 作为产后脂肪扩张所需的脂肪生成共激活剂的细胞和基因特异性调节作用。