c-Myb and Ets proteins synergize to overcome transcriptional repression by ZEB
c-Myb and Ets proteins synergize to overcome transcriptional repression by ZEB
复制标题
DOI：
10.1093/emboj/16.13.3924
复制
发表时间：
1997-07-01
期刊：
影响因子：
11.4
通讯作者：
Dean, DC
中科院分区：
文献类型：
--
作者：
Postigo, AA;Sheppard, AM;Dean, DC
Zfh家族的锌指/同源域蛋白首先在果蝇中被发现，它是中枢神经系统和肌肉等组织分化所必需的，Zeb是Zfh-1的脊椎动物同源物，它结合E盒的一个子集并通过转录抑制肌肉基因来阻断肌肉的发生。我们在这里提供了证据，Zeb在控制造血基因转录方面也有重要的作用，正常造血所需的两个转录因子家族是c-Myb和Ets。这些因子协同作用激活转录，这种协同作用是至少几个重要的造血基因转录所必需的。Zeb单独阻断c-Myb和Ets的活性，但这两个因素协同作用来抵抗这种抑制。这种抑制对c-Myb和ETS的转录活性都有要求，这为为什么这些因素之间的协同作用很重要提供了一种解释。Zeb抑制和c-Myb/ETS转录激活之间的平衡为控制造血细胞的基因表达提供了一种灵活的调控机制。我们证明，体内这种正/负调控的一个靶点是α4整合素，它在正常的造血和成熟白细胞的功能中起着关键作用。
The Zfh family of zinc finger/homeodomain proteins was first identified in Drosophila where it is required for differentiation of tissues such as the central nervous system and muscle, ZEB, a vertebrate homolog of Zfh-1, binds a subset of E boxes and blocks myogenesis through transcriptional repression of muscle genes, We present evidence here that ZEB also has an important role in controlling hematopoietic gene transcription, Two families of transcription factors that are required for normal hematopoiesis are c-Myb and Ets. These factors act synergistically to activate transcription, and this synergy is required for transcription of at least several important hematopoietic genes. ZEB blocks the activity of c-Myb and Ets individually, but together the factors synergize to resist this repression. Such repression imposes a requirement for both c-Myb and Ets for transcriptional activity, providing one explanation for why synergy between these factors is important. The balance between repression by ZEB and transcriptional activation by c-Myb/Ets provides a flexible regulatory mechanism for controlling gene expression in hematopoietic cells. We demonstrate that one target of this positive/negative regulation in vivo is the alpha 4 integrin, which play a key role in normal hematopoiesis and function of mature leukocytes.