The Co-operation of RUNX1 with LDB1, CDK9 and BRD4 Drives Transcription Factor Complex Relocation During Haematopoietic Specification.
The Co-operation of RUNX1 with LDB1, CDK9 and BRD4 Drives Transcription Factor Complex Relocation During Haematopoietic Specification.
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DOI：
10.1038/s41598-018-28506-7
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发表时间：
2018-07-10
影响因子：
4.6
通讯作者：
Bonifer C
中科院分区：
文献类型：
--
作者：
Gilmour J;Assi SA;Noailles L;Lichtinger M;Obier N;Bonifer C
造血细胞通过一种被称为内皮-造血学转变(EHT)的过程从胚胎背主动脉内的内皮细胞中产生。这一过程关键依赖于转录因子RUNX1，它能迅速激活造血发育所必需的基因的表达。在小鼠胚胎干细胞分化模型中使用RUNX1的诱导版本，我们表明在EHT之前，造血基因由转录因子FLI1的结合而启动。一旦表达，RUNX1就将FLI1重新定位到它的结合部位。然而，RUNX1招募的转录因子组件的性质尚不清楚，这些转录因子组件用于重塑染色质景观和启动mRNA合成。在这里，我们对依赖于RUNX1的转录延伸相关因子的结合进行了全基因组分析来解决这个问题。我们证明了RUNX1的诱导将FLI1从Ets/GATA末端转移到RUNX1/Ets，并招募了基本转录因子CDK9、BRD4、中介复合体和循环因子LDB1。我们的研究解释了单个转录因子的表达如何驱动细胞形状的快速和复制无关的转变，这在发育和疾病中被广泛观察到。
Haematopoietic cells arise from endothelial cells within the dorsal aorta of the embryo via a process called the endothelial-haematopoietic transition (EHT). This process crucially depends on the transcription factor RUNX1 which rapidly activates the expression of genes essential for haematopoietic development. Using an inducible version of RUNX1 in a mouse embryonic stem cell differentiation model we showed that prior to the EHT, haematopoietic genes are primed by the binding of the transcription factor FLI1. Once expressed, RUNX1 relocates FLI1 towards its binding sites. However, the nature of the transcription factor assemblies recruited by RUNX1 to reshape the chromatin landscape and initiate mRNA synthesis are unclear. Here, we performed genome-wide analyses of RUNX1-dependent binding of factors associated with transcription elongation to address this question. We demonstrate that RUNX1 induction moves FLI1 from distal ETS/GATA sites to RUNX1/ETS sites and recruits the basal transcription factors CDK9, BRD4, the Mediator complex and the looping factor LDB1. Our study explains how the expression of a single transcription factor can drive rapid and replication independent transitions in cellular shape which are widely observed in development and disease.
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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：
64.8
作者：
Chen, Michael J.;Yokomizo, Tomomasa;Zeigler, Brandon M.;Dzierzak, Elaine;Speck, Nancy A.
通讯作者：
Speck, Nancy A.
DOI：
10.1242/dev.139857
发表时间：
2016-12-01
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Obier N;Cauchy P;Assi SA;Gilmour J;Lie-A-Ling M;Lichtinger M;Hoogenkamp M;Noailles L;Cockerill PN;Lacaud G;Kouskoff V;Bonifer C
通讯作者：
Bonifer C
DOI：
10.2741/3977
发表时间：
2012-01-01
期刊：
Frontiers in bioscience (Landmark edition)
影响因子：
--
作者：
Lam K;Zhang DE
通讯作者：
Zhang DE
DOI：
10.1242/dev.106054
发表时间：
2014-06
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Gilmour J;Assi SA;Jaegle U;Kulu D;van de Werken H;Clarke D;Westhead DR;Philipsen S;Bonifer C
通讯作者：
Bonifer C