Cooperative regulation of Zhx1 and hnRNPA1 drives the cardiac progenitor-specific transcriptional activation during cardiomyocyte differentiation.
Cooperative regulation of Zhx1 and hnRNPA1 drives the cardiac progenitor-specific transcriptional activation during cardiomyocyte differentiation.
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Zhx1和hnRNPA1的协同调节驱动心肌细胞分化过程中心脏祖细胞特异性转录激活
DOI：
10.1038/s41420-023-01548-1
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发表时间：
2023-07-14
影响因子：
7
通讯作者：
Guo, Xudong
中科院分区：
文献类型：
--
作者：
Chen, Yang;Wu, Yukang;Li, Jianguo;Chen, Kai;Wang, Wuchan;Ye, Zihui;Feng, Ke;Yang, Yiwei;Xu, Yanxin;Kang, Jiuhong;Guo, Xudong
锌指蛋白（ZNF）介导的转录调控在细胞命运转换中起着关键作用。然而，目前尚不清楚ZNFs如何实现其特定的调节作用，在特定阶段的心肌细胞分化的决定。在这里，我们报道了锌指和同源异型盒1（Zhx 1）蛋白，在细胞命运从中胚层到心脏祖细胞的过渡过程中瞬时表达，是小鼠和人胚胎干细胞的心肌细胞分化所不可或缺的。此外，Zhx 1主要通过与hnRNPA 1相互作用促进心脏祖细胞的特化，并共激活广泛基因的转录。深入的机制研究表明，Zhx 1通过第二个Znf结构域的氨基酸残基（Thr 111-His 120）与hnRNPA 1结合，从而参与心脏祖细胞的形成。总之，我们的研究强调了Zhx 1/hnRNPA 1在心脏祖细胞特化过程中激活基因转录的未揭示的相互作用，也为心肌细胞分化中细胞命运决定的特异性提供了新的证据。
The zinc finger proteins (ZNFs) mediated transcriptional regulation is critical for cell fate transition. However, it is still unclear how the ZNFs realize their specific regulatory roles in the stage-specific determination of cardiomyocyte differentiation. Here, we reported that the zinc fingers and homeoboxes 1 (Zhx1) protein, transiently expressed during the cell fate transition from mesoderm to cardiac progenitors, was indispensable for the proper cardiomyocyte differentiation of mouse and human embryonic stem cells. Moreover, Zhx1 majorly promoted the specification of cardiac progenitors via interacting with hnRNPA1 and co-activated the transcription of a wide range of genes. In-depth mechanistic studies showed that Zhx1 was bound with hnRNPA1 by the amino acid residues (Thr111–His120) of the second Znf domain, thus participating in the formation of cardiac progenitors. Together, our study highlights the unrevealed interaction of Zhx1/hnRNPA1 for activating gene transcription during cardiac progenitor specification and also provides new evidence for the specificity of cell fate determination in cardiomyocyte differentiation.
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