Gata2, Fli1, and Scl form a recursively wired gene-regulatory circuit during early hematopoietic development
Gata2, Fli1, and Scl form a recursively wired gene-regulatory circuit during early hematopoietic development
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DOI：
10.1073/pnas.0707045104
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发表时间：
2007-11-06
影响因子：
11.1
通讯作者：
Gottgens, Berthold
中科院分区：
文献类型：
--
作者：
Pimanda, John E.;Ottersbach, Katrin;Gottgens, Berthold
脊椎动物体型的保守性归因于基因调控网络（GRNs）的进化稳定性。我们描述了一个由Gata 2，Fli 1和Scl/Tal 1及其增强子Gata 2 -3，Fli 1 +12和Sc/+19组成的调节回路，该回路在小鼠胚胎造血的特化过程中起作用。我们发现Fli 1 +12增强子与Gata 2 -3和Scl+19增强子一样，靶向造血干细胞（HSC），并依赖于Ets、加塔和E-Box基序的组合。我们发现Gata 2 -3增强子也使用类似的基序簇，并且Gata 2，Fli 1和Scl在胚胎第11.5天的背主动脉中表达，其中HSCs起源于胎肝，并且在胎肝中繁殖。这些组织和ES细胞衍生的成血管细胞等同物中的三个HSC增强子被这些转录因子（TF）中的每一个结合，并形成完全连接的三联体，其构成了哺乳动物发育中的这种网络基序和在哺乳动物干细胞的特化期间操作的GRN内核的先前未描述的实例。
Conservation of the vertebrate body plan has been attributed to the evolutionary stability of gene-regulatory networks (GRNs). We describe a regulatory circuit made up of Gata2, Fli1, and Scl/Tal1 and their enhancers, Gata2-3, Fli1+12, and Sc/+19, that operates during specification of hematopoiesis in the mouse embryo. We show that the Fli1+12 enhancer, like the Gata2-3 and Scl+19 enhancers, targets hematopoietic stem cells (HSCs) and relies on a combination of Ets, Gata, and E-Box motifs. We show that the Gata2-3 enhancer also uses a similar cluster of motifs and that Gata2, Fli1, and Scl are expressed in embryonic day-11.5 dorsal aorta where HSCs originate and in fetal liver where they multiply. The three HSC enhancers in these tissues and in ES cell-derived hemangioblast equivalents are bound by each of these transcription factors (TFs) and form a fully connected triad that constitutes a previously undescribed example of both this network motif in mammalian development and a GRN kernel operating during the specification of a mammalian stem cell.