High-mobility group protein HMGB2 regulates human erythroid differentiation through trans-activation of GFI1B transcription
High-mobility group protein HMGB2 regulates human erythroid differentiation through trans-activation of GFI1B transcription
复制标题
DOI：
10.1182/blood-2009-06-230094
复制
发表时间：
2010-01-21
期刊：
影响因子：
20.3
通讯作者：
Dumenil, Dominique
中科院分区：
文献类型：
--
作者：
Laurent, Benoit;Randrianarison-Huetz, Voahangy;Dumenil, Dominique
GFI-1B是一种转录抑制因子，对红细胞分化至关重要：小鼠中GFI 1B基因的失活会导致胚胎死亡，原因是无法产生分化的红细胞。因此，GFI 1B表达在红细胞生成过程中受到严格调控，但参与这种调控的机制仍有部分了解。我们在这里确定HMGB 2，高迁移率族HMG蛋白，作为GFI 1B转录的关键调节因子。HMGB 2在体内与GFI 1B启动子结合，并上调其反式激活，最有可能是通过增强Oct-1与GFI 1B启动子的结合，以及在较小程度上增强加塔-1和NF-Y与GFI 1B启动子的结合。在红系分化过程中，HMGB 2的表达随着GfI 1B转录的增加而增加。重要的是，在未成熟造血祖细胞中敲低HMGB 2导致Gfi-1B表达降低并损害其红系分化。我们认为HMGB 2通过Oct-1增强GFI 1B的加塔-1依赖性转录，从而控制红系分化。（血。2010; 115：687-695）
Gfi-1B is a transcriptional repressor that is crucial for erythroid differentiation: inactivation of the GFI1B gene in mice leads to embryonic death due to failure to produce differentiated red cells. Accordingly, GFI1B expression is tightly regulated during erythropoiesis, but the mechanisms involved in such regulation remain partially understood. We here identify HMGB2, a high-mobility group HMG protein, as a key regulator of GFI1B transcription. HMGB2 binds to the GFI1B promoter in vivo and up-regulates its transactivation most likely by enhancing the binding of Oct-1 and, to a lesser extent, of GATA-1 and NF-Y to the GFI1B promoter. HMGB2 expression increases during erythroid differentiation concomitantly to the increase of GfI1B transcription. Importantly, knockdown of HMGB2 in immature hematopoietic progenitor cells leads to decreased Gfi-1B expression and impairs their erythroid differentiation. We propose that HMGB2 potentiates GATA-1 dependent transcription of GFI1B by Oct-1 and thereby controls erythroid differentiation. (Blood. 2010; 115: 687-695)