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Title: | GATA2 mitotic bookmarking is required for definitive haematopoiesis | Authors: | Silvério-Alves, Rita Kurochkin, Ilia Rydström, Anna Vazquez Echegaray, Camila Haider, Jakob Nicholls, Matthew Rode, Christina Thelaus, Louise Lindgren, Aida Yifter Ferreira, Alexandra G. Brandão, Rafael Larsson, Jonas de Bruijn, Marella F. T. R. Martin-Gonzalez, Javier Pereira, Carlos Filipe |
Issue Date: | 14-Aug-2023 | Publisher: | Springer Nature | Project: | This project has received funding (C.-F.P.) from the Olle Engkvist Foundation (194- 0694), FCT (2022.02338.PTDC) and Plano de Recuperação e Resiliência de Portugal pelo fundo NextGenerationEU (C644865576-00000005). Wewould like to acknowledge the Knut and AliceWallenberg foundation, the Medical Faculty at Lund University and Region Skåne for financial support. R.S.-A received funding fromthe Royal Physiographic Society of Lund. Research in the de Bruijn group was supported by a program in the MRCMolecularHaematology UnitCore award (MC_UU_00016/02). C.V.E. is supported by aMarie Curie postdoctoral fellowship (101067501). R.S.-A and A.G.F. are supported by FCT scholarships with references PD/BD/ 135725/2018 and SFRH/BD/133233/2017, respectively. | Serial title, monograph or event: | Nature Communications | Volume: | 14 | Issue: | 1 | Abstract: | In mitosis, most transcription factors detach from chromatin, but some are retained and bookmark genomic sites. Mitotic bookmarking has been implicated in lineage inheritance, pluripotency and reprogramming. However, the biological significance of this mechanism in vivo remains unclear. Here, we address mitotic retention of the hemogenic factors GATA2, GFI1B and FOS during haematopoietic specification. We show that GATA2 remains bound to chromatin throughout mitosis, in contrast to GFI1B and FOS, via C-terminal zinc finger-mediated DNA binding. GATA2 bookmarks a subset of its interphase targets that are co-enriched for RUNX1 and other regulators of definitive haematopoiesis. Remarkably, homozygous mice harbouring the cyclin B1 mitosis degradation domain upstream Gata2 partially phenocopy knockout mice. Degradation of GATA2 at mitotic exit abolishes definitive haematopoiesis at aorta-gonad-mesonephros, placenta and foetal liver, but does not impair yolk sac haematopoiesis. Our findings implicate GATA2-mediated mitotic bookmarking as critical for definitive haematopoiesis and highlight a dependency on bookmarkers for lineage commitment. | URI: | https://hdl.handle.net/10316/111612 | ISSN: | 2041-1723 | DOI: | 10.1038/s41467-023-40391-x | Rights: | openAccess |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais |
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