GATA2 mitotic bookmarking is required for definitive haematopoiesis.
GATA2 mitotic bookmarking is required for definitive haematopoiesis.
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DOI：
10.1038/s41467-023-40391-x
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发表时间：
2023-08-14
影响因子：
16.6
通讯作者：
Pereira, Carlos-Filipe
中科院分区：
文献类型：
--
作者：
Silverio-Alves, Rita;Kurochkin, Ilia;Rydstrom, Anna;Echegaray, Camila Vazquez;Haider, Jakob;Nicholls, Matthew;Rode, Christina;Thelaus, Louise;Lindgren, Aida Yifter;Ferreira, Alexandra Gabriela;Brandao, Rafael;Larsson, Jonas;de Bruijn, Marella F. T. R.;Martin-Gonzalez, Javier;Pereira, Carlos-Filipe
在有丝分裂中，大多数转录因子从染色质中分离出来，但也有一些保留下来并标记在基因组位置上。有丝分裂书签与血统遗传、多能性和重编程有关。然而，这一机制在体内的生物学意义尚不清楚。在这里，我们讨论了造血因子GATA2、GFI1B和FOS在造血规范过程中的有丝分裂保留。我们发现，与GFI1B和FOS不同，GATA2在整个有丝分裂过程中仍然与染色质结合，这是通过C端锌指介导的DNA结合实现的。GATA2标记了它的间期靶标的子集，这些靶标对RUNX1和其他最终的造血调控因子具有共同的富集性。值得注意的是，携带Cyclin B1有丝分裂降解结构域上游的Gata2部分表型敲除小鼠的纯合子小鼠。GATA2在有丝分裂退出时的降解取消了在主动脉-性腺-中肾、胎盘和胎肝的确定的造血，但不损害卵黄囊的造血。我们的发现暗示GATA2介导的有丝分裂书签对最终的造血至关重要，并强调了对书签的血统承诺的依赖。大多数转录因子在有丝分裂过程中会从染色质中分离出来，但也有一些会保留下来，并标记基因组位置。在这里，作者表明，GATA2介导的有丝分裂书签对于最终的造血至关重要。
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. 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 haematopoiesis.
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影响因子：
11.8
作者：
Goode DK;Obier N;Vijayabaskar MS;Lie-A-Ling M;Lilly AJ;Hannah R;Lichtinger M;Batta K;Florkowska M;Patel R;Challinor M;Wallace K;Gilmour J;Assi SA;Cauchy P;Hoogenkamp M;Westhead DR;Lacaud G;Kouskoff V;Göttgens B;Bonifer C
通讯作者：
Bonifer C
影响因子：
8.8
作者：
Gomes, Andreia M.;Kurochkin, Ilia;Pereira, Carlos-Filipe
通讯作者：
Pereira, Carlos-Filipe
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK
影响因子：
5.8
作者：
通讯作者：
--
DOI：
10.1084/jem.20130751
发表时间：
2013-12-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
de Pater E;Kaimakis P;Vink CS;Yokomizo T;Yamada-Inagawa T;van der Linden R;Kartalaei PS;Camper SA;Speck N;Dzierzak E
通讯作者：
Dzierzak E