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iScience. 2021 Feb 20;24(3):102210. doi: 10.1016/j.isci.2021.102210. eCollection 2021 Mar 19.

Interplay between FLI-1 and the LDB1 complex in murine erythroleukemia cells and during megakaryopoiesis.

iScience

Guillaume Giraud, Petros Kolovos, Ilias Boltsis, Jente van Staalduinen, Boris Guyot, Michele Weiss-Gayet, Wilfred van IJcken, François Morlé, Frank Grosveld

Affiliations

  1. Department of Cell Biology, Erasmus Medical Centre, 3015CN Rotterdam, the Netherlands.
  2. Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis 68100, Greece.
  3. CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
  4. Inserm U1052, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
  5. Université de Lyon, Lyon, France.
  6. Department of Immunity, Virus and Microenvironment, Lyon, France.
  7. Institut NeuroMyoGène, CNRS UMR 5310 - INSERM U1217 - Université de Lyon - Université Claude Bernard Lyon 1, Lyon, France.
  8. Biomics Center, Erasmus University Medical Center, 3015CN Rotterdam, the Netherlands.

PMID: 33733070 PMCID: PMC7940982 DOI: 10.1016/j.isci.2021.102210

Abstract

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.

© 2021 The Author(s).

Keywords: Chromosome Organization; Molecular Biology

Conflict of interest statement

The authors declare no competing of interest.

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