ZFP30 promotes adipogenesis through the KAP1-mediated activation of a retrotransposon-derived Pparg2 enhancer
ZFP30 promotes adipogenesis through the KAP1-mediated activation of a retrotransposon-derived Pparg2 enhancer
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DOI：
10.1038/s41467-019-09803-9
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发表时间：
2019-04-18
影响因子：
16.6
通讯作者：
Deplancke, Bart
中科院分区：
文献类型：
--
作者：
Chen, Wanze;Schwalie, Petra C.;Deplancke, Bart
Kruppel相关盒锌指蛋白（KZFPs）构成了哺乳动物转录因子中最大的家族，但大多数仍然完全未知。虽然最初提出主要抑制转座因子，但最近的报道显示KFZPs有助于各种各样的其他生物过程。使用小鼠和人的体外和体内模型，我们在这里证明，一个研究不足的KZFP，ZFP 30，促进脂肪形成直接靶向和激活逆转录转座子衍生的Pparg 2增强子。通过机制研究，我们进一步表明，ZFP 30招募共调节KRAB相关蛋白1（KAP 1），令人惊讶的是，它在这种脂肪形成背景下充当ZFP 30共激活剂。我们的研究结果提供了对脂肪形成和KZFP-KAP 1复合物介导的基因调控的理解，表明KZFP-KAP 1轴也可以以非抑制方式发挥作用。
Kruppel-associated box zinc finger proteins (KZFPs) constitute the largest family of mammalian transcription factors, but most remain completely uncharacterized. While initially proposed to primarily repress transposable elements, recent reports have revealed that KFZPs contribute to a wide variety of other biological processes. Using murine and human in vitro and in vivo models, we demonstrate here that one poorly studied KZFP, ZFP30, promotes adipogenesis by directly targeting and activating a retrotransposon-derived Pparg2 enhancer. Through mechanistic studies, we further show that ZFP30 recruits the co-regulator KRAB-associated protein 1 (KAP1), which, surprisingly, acts as a ZFP30 co-activator in this adipogenic context. Our findings provide an understanding of both adipogenic and KZFP-KAP1 complex-mediated gene regulation, showing that the KZFP-KAP1 axis can also function in a non-repressive manner.