GATA2 mitotic bookmarking is required for definitive haematopoiesis
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 add...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Springer Nature
2023
|
| _version_ | 1797112332199919616 |
|---|---|
| author | Silvério-Alves, R Kurochkin, I Rydström, A Vazquez Echegaray, C Haider, J Nicholls, M Rode, C Thelaus, L Lindgren, AY Ferreira, AG Brandão, R Larsson, J de Bruijn, MFTR Martin-Gonzalez, J Pereira, C-F |
| author_facet | Silvério-Alves, R Kurochkin, I Rydström, A Vazquez Echegaray, C Haider, J Nicholls, M Rode, C Thelaus, L Lindgren, AY Ferreira, AG Brandão, R Larsson, J de Bruijn, MFTR Martin-Gonzalez, J Pereira, C-F |
| author_sort | Silvério-Alves, R |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T08:22:41Z |
| format | Journal article |
| id | oxford-uuid:1714563e-4165-400c-91e4-ebd66d86a7d9 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:22:41Z |
| publishDate | 2023 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:1714563e-4165-400c-91e4-ebd66d86a7d92024-02-07T11:28:27ZGATA2 mitotic bookmarking is required for definitive haematopoiesisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1714563e-4165-400c-91e4-ebd66d86a7d9EnglishSymplectic ElementsSpringer Nature2023Silvério-Alves, RKurochkin, IRydström, AVazquez Echegaray, CHaider, JNicholls, MRode, CThelaus, LLindgren, AYFerreira, AGBrandão, RLarsson, Jde Bruijn, MFTRMartin-Gonzalez, JPereira, C-FIn 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. |
| spellingShingle | Silvério-Alves, R Kurochkin, I Rydström, A Vazquez Echegaray, C Haider, J Nicholls, M Rode, C Thelaus, L Lindgren, AY Ferreira, AG Brandão, R Larsson, J de Bruijn, MFTR Martin-Gonzalez, J Pereira, C-F GATA2 mitotic bookmarking is required for definitive haematopoiesis |
| title | GATA2 mitotic bookmarking is required for definitive haematopoiesis |
| title_full | GATA2 mitotic bookmarking is required for definitive haematopoiesis |
| title_fullStr | GATA2 mitotic bookmarking is required for definitive haematopoiesis |
| title_full_unstemmed | GATA2 mitotic bookmarking is required for definitive haematopoiesis |
| title_short | GATA2 mitotic bookmarking is required for definitive haematopoiesis |
| title_sort | gata2 mitotic bookmarking is required for definitive haematopoiesis |
| work_keys_str_mv | AT silverioalvesr gata2mitoticbookmarkingisrequiredfordefinitivehaematopoiesis AT kurochkini gata2mitoticbookmarkingisrequiredfordefinitivehaematopoiesis AT rydstroma gata2mitoticbookmarkingisrequiredfordefinitivehaematopoiesis AT vazquezechegarayc gata2mitoticbookmarkingisrequiredfordefinitivehaematopoiesis AT haiderj gata2mitoticbookmarkingisrequiredfordefinitivehaematopoiesis AT nichollsm gata2mitoticbookmarkingisrequiredfordefinitivehaematopoiesis AT rodec gata2mitoticbookmarkingisrequiredfordefinitivehaematopoiesis AT thelausl gata2mitoticbookmarkingisrequiredfordefinitivehaematopoiesis AT lindgrenay gata2mitoticbookmarkingisrequiredfordefinitivehaematopoiesis AT ferreiraag gata2mitoticbookmarkingisrequiredfordefinitivehaematopoiesis AT brandaor gata2mitoticbookmarkingisrequiredfordefinitivehaematopoiesis AT larssonj gata2mitoticbookmarkingisrequiredfordefinitivehaematopoiesis AT debruijnmftr gata2mitoticbookmarkingisrequiredfordefinitivehaematopoiesis AT martingonzalezj gata2mitoticbookmarkingisrequiredfordefinitivehaematopoiesis AT pereiracf gata2mitoticbookmarkingisrequiredfordefinitivehaematopoiesis |