GATA2 Mitotic Bookmarking Is Required for Definitive Haematopoiesis
August 14, 2023
Rita Silvério-Alves, Ilia Kurochkin, Anna Rydström, Camila Vazquez Echegaray, Jakob Haider, Matthew Nicholls, Christina Rode, Louise Thelaus, Aida Yifter Lindgren, Alexandra Gabriela Ferreira, Rafael Brandão, Jonas Larsson, Marella de Bruijn, Javier Martin-Gonzalez, Carlos-Filipe Pereira
Related Data:ChIP-Seq for GATA2 in asynchronous and mitotic K562 cells Single-Cell RNA-Seq of hemogenic reprogramming with MD-GATA2 or MDmut-GATA2 in combination with GFI1B and FOS in HDFs
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 hematopoietic 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 highlights a dependency on bookmarkers for lineage commitment.
Genome Browser for ChIP-Seq
Most transcription factors detach from chromatin during mitosis, but some are retained and bookmark genomic sites. Here, the authors show that GATA2-mediated mitotic bookmarking is critical for definitive hematopoiesis.