Department of Pathology, Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital, CSIC-University of Seville, 41013 Seville, Spain.
Spanish Biomedical Research Network Centre in Oncology, CIBERONC of the Carlos III Health Institute (ISCIII), 28029 Madrid, Spain.
Int J Mol Sci. 2022 Apr 1;23(7):3920. doi: 10.3390/ijms23073920.
The transcription factor, early growth response-1 (EGR-1), is involved in the regulation of cell differentiation, proliferation, and apoptosis in response to different stimuli. EGR-1 is described to be involved in pancreatic endoderm differentiation, but the regulatory mechanisms controlling its action are not fully elucidated. Our previous investigation reported that exposure of mouse embryonic stem cells (mESCs) to the chemical nitric oxide (NO) donor diethylenetriamine nitric oxide adduct (DETA-NO) induces the expression of early differentiation genes such as pancreatic and duodenal homeobox 1 (). We have also evidenced that expression is associated with the release of polycomb repressive complex 2 (PRC2) and P300 from the promoter; these events were accompanied by epigenetic changes to histones and site-specific changes in the DNA methylation. Here, we investigate the role of EGR-1 on regulation in mESCs. This study reveals that EGR-1 plays a negative role in expression and shows that the binding capacity of EGR-1 to the promoter depends on the methylation level of its DNA binding site and its acetylation state. These results suggest that targeting EGR-1 at early differentiation stages might be relevant for directing pluripotent cells into -dependent cell lineages.
转录因子早期生长反应因子-1（EGR-1）参与细胞分化、增殖和凋亡的调节，以响应不同的刺激。EGR-1 被描述为参与胰腺内胚层分化，但控制其作用的调节机制尚未完全阐明。我们之前的研究报告称，暴露于化学一氧化氮（NO）供体二亚乙基三胺一氧化氮加合物（DETA-NO）的小鼠胚胎干细胞（mESCs）诱导胰腺和十二指肠同源盒 1（）等早期分化基因的表达。我们还证明，表达与多梳抑制复合物 2（PRC2）和 P300 从 启动子的释放有关；这些事件伴随着组蛋白的表观遗传变化和 DNA 甲基化的特异性变化。在这里，我们研究了 EGR-1 在 mESCs 中对 调节的作用。这项研究表明，EGR-1 在 表达中起负调控作用，并表明 EGR-1 与 启动子结合的能力取决于其 DNA 结合位点的甲基化水平及其乙酰化状态。这些结果表明，在早期分化阶段靶向 EGR-1 可能与指导多能细胞进入 依赖性细胞谱系有关。
