POU homeodomain protein OCT1 modulates islet 1 expression during cardiac differentiation of P19CL6 cells
POU homeodomain protein OCT1 modulates islet 1 expression during cardiac differentiation of P19CL6 cells
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POU同源域蛋白OCT1调节P19CL6细胞心脏分化过程中胰岛1的表达
DOI：
10.1007/s00018-010-0544-y
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发表时间：
2011-06-01
影响因子：
8
通讯作者：
Zhou, Chunyan
中科院分区：
文献类型：
--
作者：
Liu, Yinan;Li, Yanming;Zhou, Chunyan
胰岛1（Islet 1，ISL 1）是心脏祖细胞的标志物，在心脏发生中起着重要作用。然而，激活其表达的确切机制尚未完全了解。利用P19CL6细胞心肌分化模型，我们发现POU同源结构域蛋白OCT1在心肌分化过程中调节Isl1的表达，OCT1敲低可导致Isl1表达减少，并下调中胚层、心脏特异性和信号通路基因的表达。此外，位于Isl 1启动子近端区域的八聚体基序对Isl 1的转录激活是必需的。该基序的突变显著降低Isl1转录。尽管OCT 1和OCT 4都与该基序结合，但调控Isl1表达的是OCT 1而不是OCT 4。此外，在早期胚胎中，原位杂交揭示了OCT 1在调控Isl 1中的相关性。总的来说，我们的数据突出了OCT 1在Isl1表达调控中的新作用。
Islet 1 (ISL1), a marker of cardiac progenitors, plays a crucial role in cardiogenesis. However, the precise mechanism underlying the activation of its expression is not fully understood. Using the cardiac differentiation model of P19CL6 cells, we show that POU homeodomain protein, OCT1, modulatesIsl1expression in the process of cardiac differentiation.Oct1knock-down resulted in reduction ofIsl1expression and downregulated mesodermal, cardiac-specific, and signal pathway gene expression. Additionally, the octamer motif located in the proximal region ofIsl1promoter is essential toIsl1transcriptional activation. Mutation of this motif remarkably decreasedIsl1transcription. Although both OCT1 and OCT4 bound to this motif, it was OCT1 rather than OCT4 that modulatedIsl1expression. Furthermore, the correlation of OCT1 in regulation ofIsl1was revealed by in situ hybridization in early embryos. Collectively, our data highlight a novel role of OCT1 in the regulation ofIsl1expression.