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

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^*

^*Corresponding author for this work

Cell biology

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Article number	102210
Journal	iScience
Volume	24
Issue number	3
Early online date	20 Feb 2021
DOIs	https://doi.org/10.1016/j.isci.2021.102210
Publication status	Published - 19 Mar 2021

Bibliographical note

Funding Information:
The authors acknowledge all the members of the Cell Biology Department at the Erasmus Medical Center for fruitful discussion. The authors acknowledge the members of the Biomics Department at the Erasmus Medical Center for the sequencing data. The authors also acknowledge the members of the animal house facility at the Erasmus Medical Center for taking care of the mice. This work was supported by the EU grants Syboss (GG) and Thalamos (PK) and a BIG grant (Erasmus MC) to FG. Conceptualization, G.G. and F.G.; Methodology, G.G. P.K. F.G. I.B.; Software, P.K.; Validation, G.G. and I.B.; Formal Analysis, G.G. P.K. I.B. J.v.S. M.W.G, and B.G. Investigation, G.G. and I.B.; Resources, G.G. and F.G.; Data Curation, G.G. and F.G.; Writing?Original draft, G.G.; Writing?Review & Editing, F.G. P.K. and I.B.; Visualization, G.G. and I.B. Supervision, G.G. and F.G. Project Administration; G.G. and F.G.; Funding Acquisition, F.G. The authors declare no competing of interest.

Publisher Copyright:
© 2021 The Author(s)

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Interplay between FLI-1 and the LDB1 complex in murine erythroleukemia cells and during megakaryopoiesisFinal published version, 6.57 MBLicence: CC BY

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title = "Interplay between FLI-1 and the LDB1 complex in murine erythroleukemia cells and during megakaryopoiesis",

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.",

author = "Guillaume Giraud and Petros Kolovos and Ilias Boltsis and {van Staalduinen}, Jente and Boris Guyot and Michele Weiss-Gayet and IJcken, {Wilfred van} and Fran{\c c}ois Morl{\'e} and Frank Grosveld",

note = "Funding Information: The authors acknowledge all the members of the Cell Biology Department at the Erasmus Medical Center for fruitful discussion. The authors acknowledge the members of the Biomics Department at the Erasmus Medical Center for the sequencing data. The authors also acknowledge the members of the animal house facility at the Erasmus Medical Center for taking care of the mice. This work was supported by the EU grants Syboss (GG) and Thalamos (PK) and a BIG grant (Erasmus MC) to FG. Conceptualization, G.G. and F.G.; Methodology, G.G. P.K. F.G. I.B.; Software, P.K.; Validation, G.G. and I.B.; Formal Analysis, G.G. P.K. I.B. J.v.S. M.W.G, and B.G. Investigation, G.G. and I.B.; Resources, G.G. and F.G.; Data Curation, G.G. and F.G.; Writing?Original draft, G.G.; Writing?Review & Editing, F.G. P.K. and I.B.; Visualization, G.G. and I.B. Supervision, G.G. and F.G. Project Administration; G.G. and F.G.; Funding Acquisition, F.G. The authors declare no competing of interest. Publisher Copyright: {\textcopyright} 2021 The Author(s)",

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T1 - Interplay between FLI-1 and the LDB1 complex in murine erythroleukemia cells and during megakaryopoiesis

AU - Giraud, Guillaume

AU - Kolovos, Petros

AU - Boltsis, Ilias

AU - van Staalduinen, Jente

AU - Guyot, Boris

AU - Weiss-Gayet, Michele

AU - IJcken, Wilfred van

AU - Morlé, François

AU - Grosveld, Frank

N1 - Funding Information: The authors acknowledge all the members of the Cell Biology Department at the Erasmus Medical Center for fruitful discussion. The authors acknowledge the members of the Biomics Department at the Erasmus Medical Center for the sequencing data. The authors also acknowledge the members of the animal house facility at the Erasmus Medical Center for taking care of the mice. This work was supported by the EU grants Syboss (GG) and Thalamos (PK) and a BIG grant (Erasmus MC) to FG. Conceptualization, G.G. and F.G.; Methodology, G.G. P.K. F.G. I.B.; Software, P.K.; Validation, G.G. and I.B.; Formal Analysis, G.G. P.K. I.B. J.v.S. M.W.G, and B.G. Investigation, G.G. and I.B.; Resources, G.G. and F.G.; Data Curation, G.G. and F.G.; Writing?Original draft, G.G.; Writing?Review & Editing, F.G. P.K. and I.B.; Visualization, G.G. and I.B. Supervision, G.G. and F.G. Project Administration; G.G. and F.G.; Funding Acquisition, F.G. The authors declare no competing of interest. Publisher Copyright: © 2021 The Author(s)

PY - 2021/3/19

Y1 - 2021/3/19

N2 - 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.

AB - 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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U2 - 10.1016/j.isci.2021.102210

DO - 10.1016/j.isci.2021.102210

M3 - Article

AN - SCOPUS:85101959119

VL - 24

JO - iScience

JF - iScience

IS - 3

M1 - 102210

ER -

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

Abstract

Bibliographical note

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