Giraud Guillaume, Kolovos Petros, Boltsis Ilias, van Staalduinen Jente, Guyot Boris, Weiss-Gayet Michele, IJcken Wilfred van, Morlé François, Grosveld Frank
Department of Cell Biology, Erasmus Medical Centre, 3015CN Rotterdam, the Netherlands.
Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis 68100, Greece.
iScience. 2021 Feb 20;24(3):102210. doi: 10.1016/j.isci.2021.102210. eCollection 2021 Mar 19.
Transcription factors are key players in a broad range of cellular processes such as cell-fate decision. Understanding how they act to control these processes is of critical importance for therapy purposes. FLI-1 controls several hematopoietic lineage differentiation including megakaryopoiesis and erythropoiesis. Its aberrant expression is often observed in cancer and is associated with poor prognosis. We showed that FLI-1 interacts with the LDB1 complex, which also plays critical roles in erythropoiesis and megakaryopoiesis. In this study, we aimed to unravel how FLI-1 and the LDB1 complex act together in murine erythroleukemia cells and in megakaryocyte. Combining omics techniques, we show that FLI-1 enables the recruitment of the LDB1 complex to regulatory sequences of megakaryocytic genes and to enhancers. We show as well for the first time that FLI-1 is able to modulate the 3D chromatin organization by promoting chromatin looping between enhancers and promoters most likely through the LDB1 complex.
转录因子是广泛细胞过程（如细胞命运决定）中的关键参与者。了解它们如何发挥作用来控制这些过程对于治疗目的至关重要。FLI-1控制多种造血谱系分化，包括巨核细胞生成和红细胞生成。其异常表达在癌症中经常被观察到，并且与预后不良相关。我们发现FLI-1与LDB1复合物相互作用，该复合物在红细胞生成和巨核细胞生成中也起着关键作用。在本研究中，我们旨在阐明FLI-1和LDB1复合物在小鼠红白血病细胞和巨核细胞中如何共同发挥作用。结合组学技术，我们表明FLI-1能够使LDB1复合物募集到巨核细胞基因的调控序列和增强子上。我们还首次表明，FLI-1最有可能通过LDB1复合物促进增强子与启动子之间的染色质环化，从而调节三维染色质组织。
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