Interplay between SOX7 and RUNX1 regulates hemogenic endothelial fate in the yolk sac
Interplay between SOX7 and RUNX1 regulates hemogenic endothelial fate in the yolk sac
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DOI：
10.1242/dev.140970
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发表时间：
2016-12-01
期刊：
影响因子：
4.6
通讯作者：
Kouskoff, Valerie
中科院分区：
文献类型：
--
作者：
Lilly, Andrew J.;Costa, Guilherme;Kouskoff, Valerie
内皮细胞向造血细胞转化（EHT）是一个动态过程，涉及内皮细胞基因表达的关闭和造血细胞基因转录的开启。虽然调节EHT的因素在生血内皮（HE）的背主动脉已经比较好的研究，卵黄囊HE的分子调控仍然知之甚少。在这里，我们发现SOX 7抑制HE中RUNX 1靶基因的表达，而对RUNX 1表达本身没有影响。我们确定SOX 7直接与RUNX 1相互作用并抑制其转录活性。通过这种相互作用，我们证明了SOX 7阻碍RUNX 1 DNA结合以及RUNX 1与其辅因子CBF β之间的相互作用。最后，我们通过单细胞表达谱和免疫荧光显示，与SOX 17相比，SOX 7在RUNX 1（+）卵黄囊HE群体中广泛表达。总的来说，这些数据首次证明了内皮和造血转录因子之间的直接蛋白质-蛋白质相互作用如何在HE分化和EHT期间调节对比转录程序。
Endothelial to hematopoietic transition (EHT) is a dynamic process involving the shutting down of endothelial gene expression and switching on of hematopoietic gene transcription. Although the factors regulating EHT in hemogenic endothelium (HE) of the dorsal aorta have been relatively well studied, the molecular regulation of yolk sac HE remains poorly understood. Here, we show that SOX7 inhibits the expression of RUNX1 target genes in HE, while having no effect on RUNX1 expression itself. We establish that SOX7 directly interacts with RUNX1 and inhibits its transcriptional activity. Through this interaction we demonstrate that SOX7 hinders RUNX1 DNA binding as well as the interaction between RUNX1 and its co-factor CBF beta. Finally, we show by single-cell expression profiling and immunofluorescence that SOX7 is broadly expressed across the RUNX1(+) yolk sac HE population compared with SOX17. Collectively, these data demonstrate for the first time how direct protein-protein interactions between endothelial and hematopoietic transcription factors regulate contrasting transcriptional programs during HE differentiation and EHT.