Zrf1 controls mesoderm lineage genes and cardiomyocyte differentiation
Zrf1 controls mesoderm lineage genes and cardiomyocyte differentiation
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DOI：
10.1080/15384101.2016.1245246
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发表时间：
2016-01-01
期刊：
影响因子：
4.3
通讯作者：
Richly, Holger
中科院分区：
文献类型：
--
作者：
Kaymak, Ayseguel;Richly, Holger
在本研究中，我们解决了转录激活因子Zrf1在体外发育过程中的3个胚层的产生的功能。目前，Zrf1被认为是驱动神经元基因表达的因子。在这里，我们使用小鼠胚胎干细胞和P19细胞来了解Zrf1在中胚层衍生组织如脂肪细胞、软骨和心脏的生成中的作用。我们的数据表明，Zrf1是必不可少的转录激活的基因，引起中胚层，特别是心脏的发展。在mESC和P19系统中，我们提供了Zrf1有助于功能性心肌细胞生成的证据。我们进一步证明，Zrf1结合到心脏组织特异性基因的转录起始位点（TSS）从第一和第二心脏领域，它驱动他们的时间表达在分化过程中。两者合计，我们已经确定了Zrf1作为一种新的调节器的中胚层谱系，可能有利于基因的时空表达。
In the present study we addressed the function of the transcriptional activator Zrf1 in the generation of the 3 germ layers during in vitro development. Currently, Zrf1 is rather regarded as a factor that drives the expression of neuronal genes. Here, we have employed mouse embryonic stem cells and P19 cells to understand the role of Zrf1 in the generation of mesoderm-derived tissues like adipocytes, cartilage and heart. Our data shows that Zrf1 is essential for the transcriptional activation of genes that give rise to mesoderm and in particular heart development. In both, the mESC and P19 systems, we provide evidence that Zrf1 contributes to the generation of functional cardiomyocytes. We further demonstrate that Zrf1 binds to the transcription start sites (TSSs) of heart tissue-specific genes from the first and second heart field where it drives their temporal expression during differentiation. Taken together, we have identified Zrf1 as a novel regulator of the mesodermal lineage that might facilitate spatiotemporal expression of genes.