SCF induces γ-globin gene expression by regulating downstream transcription factor COUP-TFII
SCF induces γ-globin gene expression by regulating downstream transcription factor COUP-TFII
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DOI：
10.1182/blood-2008-07-170712
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发表时间：
2009-07-02
期刊：
影响因子：
20.3
通讯作者：
Rodgers, Griffin P.
中科院分区：
文献类型：
--
作者：
Aerbajinai, Wulin;Zhu, Jianqiong;Rodgers, Griffin P.
Increased fetal hemoglobin expression in adulthood is associated with acute stress erythropoiesis. However, the mechanisms underlying gamma-globin induction during the rapid expansion of adult erythroid progenitor cells have not been fully elucidated. Here, we examined COUP-TFII as a potential repressor of gamma-globin gene after stem cell factor (SCF) stimulation in cultured human adult erythroid progenitor cells. We found that COUP-TFII expression is suppressed by SCF through phosphorylation of serine/threonine phosphatase (PP2A) and correlated well with fetal hemoglobin induction. Furthermore, down-regulation of COUP-TFII expression with small interfering RNA (siRNA) significantly increases the gamma-globin expression during the erythroid maturation. Moreover, SCF-increased expression of NF-YA associated with redox regulator Ref-1 and cellular reducing condition enhances the effect of SCF on gamma-globin expression. Activation of Erk1/2 plays a critical role in SCF modulation of downstream transcriptional factor COUP-TFII, which is involved in the regulation of gamma-globin gene induction. Our data show that SCF stimulates Erk1/2 MAPK signaling pathway, which regulates the downstream repressor COUP-TFII by inhibiting serine/threonine phosphatase 2A activity, and that decreased COUP-TFII expression resulted in gamma-globin reactivation in adult erythropoiesis. These observations provide insight into the molecular pathways that regulate gamma-globin augmentation during stress erythropoiesis. (Blood. 2009;114:187-194)
