Maf1 and Repression of RNA Polymerase III-Mediated Transcription Drive Adipocyte Differentiation.
Maf1 and Repression of RNA Polymerase III-Mediated Transcription Drive Adipocyte Differentiation.
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DOI：
10.1016/j.celrep.2018.07.046
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发表时间：
2018-08-14
期刊：
影响因子：
8.8
通讯作者：
Johnson DL
中科院分区：
文献类型：
--
作者：
Chen CY;Lanz RB;Walkey CJ;Chang WH;Lu W;Johnson DL
RNA聚合酶（pol） III转录多种参与转录、RNA加工和翻译的小的未翻译RNA。RNA pol III及其组分在各种人类发育障碍中发生改变，但它们在细胞命运决定和发育中的作用尚不清楚。在这里，我们证明了Maf1，一个转录抑制因子，促进小鼠胚胎干细胞（mESCs）向中胚层的诱导。mESCs和前脂肪细胞中Maf1表达的减少会损害脂肪形成，而在Maf1缺失的细胞中异位表达则会促进分化。通过化学抑制或敲低Brf1来抑制RNA pol III可促进脂肪形成。改变的RNA pol iii依赖转录产生mrna的选择性变化，显著富集脂肪基因特征。此外，RNA pol iii介导的转录正调控长链非编码RNA H19和Wnt6的表达，建立了脂肪生成抑制剂。总之，这些研究揭示了RNA pol iii介导的转录和Maf1在中胚层诱导和脂肪细胞分化中的重要和意想不到的功能。Maf1和RNA pol III转录抑制通过促进中胚层诱导和脂肪细胞分化，在细胞命运决定中起关键作用。Chen等人的研究表明，RNA pol III转录的改变会导致脂肪生成基因的选择性改变，以及包括Wnt6和H19lnc RNA在内的抑制因子，从而调控脂肪生成。
RNA polymerase (pol) III transcribes a variety of small untranslated RNAs involved in transcription, RNA processing, and translation. RNA pol III and its components are altered in various human developmental disorders, yet their roles in cell fate determination and development are poorly understood. Here we demonstrate that Maf1, a transcriptional repressor, promotes induction of mouse embryonic stem cells (mESCs) into mesoderm. Reduced Maf1 expression in mESCs and preadipocytes impairs adipogenesis, while ectopic Maf1 expression in Maf1-deficient cells enhances differentiation. RNA pol III repression by chemical inhibition or knockdown of Brf1 promotes adipogenesis. Altered RNA pol III-dependent transcription produces select changes in mRNAs with a significant enrichment of adipogenic gene signatures. Furthermore, RNA pol III-mediated transcription positively regulates long non-coding RNA H19 and Wnt6 expression, established adipogenesis inhibitors. Together, these studies reveal an important and unexpected function for RNA pol III-mediated transcription and Maf1 in mesoderm induction and adipocyte differentiation. Maf1 and RNA pol III transcription repression play a key role in cell fate determination by promoting mesoderm induction and adipocyte differentiation. Chen et al. show that alterations in RNA pol III transcription produce select changes in adipogenic genes, and inhibitory factors including Wnt6 and H19lnc RNA, to regulate adipogenesis.
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