Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
Cell Mol Life Sci. 2011 Jun;68(11):1969-82. doi: 10.1007/s00018-010-0544-y. Epub 2010 Oct 21.
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, modulates Isl1 expression in the process of cardiac differentiation. Oct1 knock-down resulted in reduction of Isl1 expression and downregulated mesodermal, cardiac-specific, and signal pathway gene expression. Additionally, the octamer motif located in the proximal region of Isl1 promoter is essential to Isl1 transcriptional activation. Mutation of this motif remarkably decreased Isl1 transcription. Although both OCT1 and OCT4 bound to this motif, it was OCT1 rather than OCT4 that modulated Isl1 expression. Furthermore, the correlation of OCT1 in regulation of Isl1 was revealed by in situ hybridization in early embryos. Collectively, our data highlight a novel role of OCT1 in the regulation of Isl1 expression.
胰岛 1 (ISL1)是心脏祖细胞的标志物,在心脏发生中起着至关重要的作用。然而,其表达激活的确切机制尚不完全清楚。使用 P19CL6 细胞的心脏分化模型,我们表明 POU 同源域蛋白 OCT1 在心脏分化过程中调节 Isl1 的表达。Oct1 敲低导致 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 Isl1 启动子近端区域的八聚体基序对于 Isl1 的转录激活至关重要。该基序的突变显著降低了 Isl1 的转录。虽然 OCT1 和 OCT4 都结合到这个基序上,但正是 OCT1 而不是 OCT4 调节 Isl1 的表达。此外,通过早期胚胎的原位杂交揭示了 OCT1 在调节 Isl1 中的相关性。总之,我们的数据强调了 OCT1 在调节 Isl1 表达中的新作用。