iScience (Mar 2021)

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

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

Journal volume & issue
Vol. 24, no. 3
p. 102210

Abstract

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Summary: 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.

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