A GATA/RUNX cis-regulatory module couples Drosophila blood cell commitment and differentiation into crystal cells
A GATA/RUNX cis-regulatory module couples Drosophila blood cell commitment and differentiation into crystal cells
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DOI：
10.1016/j.ydbio.2007.03.010
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发表时间：
2007-05-15
影响因子：
2.7
通讯作者：
Waltzer, Lucas
中科院分区：
文献类型：
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作者：
Ferjoux, Geraldine;Auge, Benoit;Waltzer, Lucas
RUNX和GATA转录因子家族的成员在从果蝇到哺乳动物的造血过程中发挥着关键作用。在果蝇中，晶体细胞造血系的形成依赖于谱系特异性RUNX因子的持续表达(LZ)及其与GATA因子蛇(SRP)的相互作用。晶体细胞是酚氧化酶原(Propos)的主要来源，酚氧化酶是黑化所必需的酶。通过分析几种昆虫Propos的启动子区域，我们确定了一个保守的GATA/RUNX顺式调控模块，该模块确保了三种果蝇Propos的晶体细胞特异性表达。我们证明，这个模块的激活需要SRP和LZ的直接结合。有趣的是，一个类似的GATA/RUNX信号在晶体细胞分化标记中过度表达，使我们能够通过对果蝇启动子区域的全基因组筛选来识别新的SRP/LZ靶基因。最后，我们发现LZ在晶体细胞中的表达也依赖于SRP/LZ通过类似模块介导的激活，这表明晶体细胞命运选择的维持和分化程序的激活是耦合的。基于我们的观察，我们认为GATA/RUNX顺式调控模块可能通过进化在造血发育过程中重复使用。(C)2007 Elsevier Inc.保留所有权利。
Members of the RUNX and GATA transcription factor families play critical roles during hematopoiesis from Drosophila to mammals. In Drosophila, the formation of the crystal cell hematopoietic lineage depends on the continuous expression of the lineage-specific RUNX factor Lozenge (Lz) and on its interaction with the GATA factor Serpent (Srp). Crystal cells are the main source of prophenoloxidases (proPOs), the enzymes required for melanization. By analyzing the promoter regions of several insect proPOs, we identify a conserved GATA/RUNX cis-regulatory module that ensures the crystal cell-specific expression of the three Drosophila melanogaster proPO. We demonstrate that activation of this module requires the direct binding of both Srp and Lz. Interestingly, a similar GATA/RUNX signature is over-represented in crystal cell differentiation markers, allowing us to identify new Srp/Lz target genes by genome-wide screening of Drosophila promoter regions. Finally, we show that the expression of lz in the crystal cells also relies on Srp/Lz-mediated activation via a similar module, indicating that crystal cell fate choice maintenance and activation of the differentiation program are coupled. Based on our observations, we propose that this GATA/RUNX cis-regulatory module may be reiteratively used during hematopoietic development through evolution. (c) 2007 Elsevier Inc. All rights reserved.