Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland; Department of Environmental and Biological Sciences, University of Eastern Finland, Joensuu, Finland.
J Steroid Biochem Mol Biol. 2019 Sep;192:105382. doi: 10.1016/j.jsbmb.2019.105382. Epub 2019 May 28.
IRF2BP2 (interferon regulatory factor-2 binding protein-2) is an uncharacterized interaction partner of glucocorticoid (GC) receptor (GR), an anti-inflammatory and metabolic transcription factor. Here, we show that GC changes the chromatin binding of IRF2BP2 in natural chromatin milieu. The GC-induced IRF2BP2-binding sites co-occur with GR binding sites and are associated with GC-induced genes. Moreover, the depletion of IRF2BP2 modulates transcription of GC-regulated genes, represses cell proliferation and increases cell movement in HEK293 cells. In A549 cells, the depletion extensively alters the responses to GC and tumor necrosis factor α (TNF), including metabolic and inflammatory pathways. Taken together, our data support the role of IRF2BP2 as a coregulator of both GR and NF-κB, potentially modulating the crosstalk between GC and TNF signaling.
IRF2BP2（干扰素调节因子 2 结合蛋白 2）是糖皮质激素（GC）受体（GR）的一个未被描述的相互作用伙伴，GR 是一种抗炎和代谢转录因子。在这里，我们表明 GC 会改变 IRF2BP2 在天然染色质环境中的染色质结合。GC 诱导的 IRF2BP2 结合位点与 GR 结合位点共同出现，并与 GC 诱导的基因相关。此外，IRF2BP2 的耗竭会调节 GC 调节基因的转录，抑制 HEK293 细胞的增殖并增加细胞运动。在 A549 细胞中，IRF2BP2 的耗竭广泛改变了对 GC 和肿瘤坏死因子 α（TNF）的反应，包括代谢和炎症途径。总之，我们的数据支持 IRF2BP2 作为 GR 和 NF-κB 的核心调节剂的作用，可能调节 GC 和 TNF 信号之间的串扰。
