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GATA2 mitotic bookmarking is required for definitive haematopoiesis

Silvério-Alves, Rita LU ; Kurochkin, Ilia LU ; Rydström, Anna LU ; Vazquez echegaray, Camila LU orcid ; Haider, Jakob LU ; Nicholls, Matthew ; Rode, Christina ; Thelaus, Louise LU ; Lindgren, Aida Yifter LU and Ferreira, Alexandra Gabriela LU orcid , et al. (2023) In Nature Communications 14(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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
14
issue
1
article number
4645
publisher
Nature Publishing Group
external identifiers
  • scopus:85168212476
  • pmid:37580379
ISSN
2041-1723
DOI
10.1038/s41467-023-40391-x
language
English
LU publication?
yes
id
ddac5686-f2ac-4b18-8bcd-0bd97cadfa7f
date added to LUP
2023-08-14 12:47:05
date last changed
2023-11-14 03:00:20
@article{ddac5686-f2ac-4b18-8bcd-0bd97cadfa7f,
  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.}},
  author       = {{Silvério-Alves, Rita and Kurochkin, Ilia and Rydström, Anna and Vazquez echegaray, Camila and Haider, Jakob and Nicholls, Matthew and Rode, Christina and Thelaus, Louise and Lindgren, Aida Yifter and Ferreira, Alexandra Gabriela and Brandão, Rafael and Larsson, Jonas and De bruijn, Marella F. T. R. and Martin-Gonzalez, Javier and Pereira, Filipe}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{GATA2 mitotic bookmarking is required for definitive haematopoiesis}},
  url          = {{http://dx.doi.org/10.1038/s41467-023-40391-x}},
  doi          = {{10.1038/s41467-023-40391-x}},
  volume       = {{14}},
  year         = {{2023}},
}