Zheng Jian, Su Guangsong, Wang Wenbin, Zhao Xueyuan, Liu Man, Bi Jinfang, Zhao Zhongfang, Shi Jiandang, Lu Wange, Zhang Lei
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
Stem Cells Dev. 2021 Jul 1;30(13):683-695. doi: 10.1089/scd.2021.0020. Epub 2021 May 24.
Homeobox B cluster () genes play important roles in retinoic acid (RA)-induced early embryonic stem cells (ESCs) differentiation. Knowledge of regulation network of is important to further unveil the mechanism of ESCs differentiation. In this study, we identified two enhancers that were activated by RA treatment and 4C data showed long-range interactions between genes and the two enhancers. CRISPR/Cas9-mediated individual or compound deletion of the two enhancers significantly inhibits gene expression, and transcriptome analysis revealed that RA-induced early ESCs differentiation was blocked in the enhancer KO cells. We propose new mechanism by which two enhancers regulate gene expression by different regulation modes during RA-induced early ESCs differentiation through long-range chromatin interactions.
同源框B簇（）基因在视黄酸（RA）诱导的早期胚胎干细胞（ESC）分化中起重要作用。了解的调控网络对于进一步揭示ESC分化机制很重要。在本研究中，我们鉴定了两个经RA处理后被激活的增强子，并且4C数据显示基因与这两个增强子之间存在长程相互作用。CRISPR/Cas9介导的两个增强子的单独或复合缺失显著抑制基因表达，转录组分析表明RA诱导的早期ESC分化在增强子敲除细胞中受阻。我们提出了一种新机制，即两个增强子在RA诱导的早期ESC分化过程中通过长程染色质相互作用以不同的调控模式调节基因表达。
