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

doi:10.1016/j.isci.2021.102210

Abstract

SummaryTranscription 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.

Highlights

Transcription factors (TF) play critical roles in a broad range of cellular processes such as cell-fate decision and proliferation
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 plays critical roles in erythropoiesis and megakaryopoiesis

Summary

Introduction

Transcription factors (TF) play critical roles in a broad range of cellular processes such as cell-fate decision and proliferation They act as protein complexes to directly regulate gene expression through their recruitment to regulatory sequences. Fli-1 has been used in combination with GATA1 and TAL1 TF to enhance megakaryocyte production from pluripotent stem cells, which has its importance in transfusion-based therapies (Moreau et al, 2016) Despite these well-established contributions of Fli-1 during physiological and pathological development, the molecular mechanisms by which this important TF acts still remain elusive

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