GABP transcription factor is required for myeloid differentiation, in part, through its control of Gfi-1 expression.
GABP transcription factor is required for myeloid differentiation, in part, through its control of Gfi-1 expression.
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DOI：
10.1182/blood-2010-07-298802
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发表时间：
2010-11
期刊：
影响因子：
20.3
通讯作者：
Zhong-fa Yang;K. Drumea;J. Cormier;Junling Wang;Xuejun Zhu;A. Rosmarin
中科院分区：
文献类型：
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作者：
Zhong-fa Yang;K. Drumea;J. Cormier;Junling Wang;Xuejun Zhu;A. Rosmarin
GABP是一种ets转录因子，调节髓样分化所需的基因。四聚体GABP复合物包括通过ets结构域结合DNA的GABPα和含有转录激活结构域的GABPβ。为了研究GABP在骨髓分化中的作用，我们产生了在造血组织中可以有条件地缺失Gabpa的小鼠。Gabpa基因敲除小鼠迅速丢失髓系细胞，残留的髓系细胞发育不良且免疫表型异常。骨髓移植表明，由于细胞内在缺陷，Gabpα null细胞不能参与骨髓腔室。Gabpa的破坏与髓系祖细胞的显著减少相关，并且Gabpα缺失的髓系细胞表达水平降低的转录抑制因子Gfi-1。Gabp结合并激活了Gfi 1启动子，用Gfi 1转导Gabpa敲除的骨髓部分挽救了髓系集落形成和髓系分化的缺陷。我们的结论是，Gabp所需的髓样分化，部分原因是它的转录抑制因子Gfi-1的调节。
GABP is an ets transcription factor that regulates genes that are required for myeloid differentiation. The tetrameric GABP complex includes GABPα, which binds DNA via its ets domain, and GABPβ, which contains the transcription activation domain. To examine the role of GABP in myeloid differentiation, we generated mice in which Gabpa can be conditionally deleted in hematopoietic tissues. Gabpa knockout mice rapidly lost myeloid cells, and residual myeloid cells were dysplastic and immunophenotypically abnormal. Bone marrow transplantation demonstrated that Gabpα null cells could not contribute to the myeloid compartment because of cell intrinsic defects. Disruption of Gabpa was associated with a marked reduction in myeloid progenitor cells, and Gabpα null myeloid cells express reduced levels of the transcriptional repressor, Gfi-1. Gabp bound and activated the Gfi1 promoter, and transduction of Gabpa knockout bone marrow with Gfi1 partially rescued defects in myeloid colony formation and myeloid differentiation. We conclude that Gabp is required for myeloid differentiation due, in part, to its regulation of the tran-scriptional repressor Gfi-1.