Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique (CNRS; Unité Mixte de Recherche [UMR] 8104), Paris, France.
Blood. 2010 Jan 21;115(3):687-95. doi: 10.1182/blood-2009-06-230094. Epub 2009 Nov 24.
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 trans-activation 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.
Gfi-1B 是一种转录抑制剂，对红细胞分化至关重要：在小鼠中，GFI1B 基因失活会导致胚胎死亡，因为无法产生分化的红细胞。因此，在红细胞生成过程中，GFI1B 的表达受到严格调控，但这种调控的机制仍部分未知。我们在这里确定了高迁移率族蛋白 2（HMGB2），一种高迁移率族 HMG 蛋白，是 GFI1B 转录的关键调节因子。HMGB2 体内结合 GFI1B 启动子，并通过增强 Oct-1 的结合（在较小程度上还增强 GATA-1 和 NF-Y 的结合）来上调其转录激活，从而上调其转录激活。HMGB2 的表达在红细胞分化过程中增加，与 GFI1B 转录的增加同时发生。重要的是，在未成熟造血祖细胞中敲低 HMGB2 会导致 Gfi-1B 表达降低，并损害其红细胞分化。我们提出，HMGB2 通过 Oct-1 增强 GATA-1 依赖性 GFI1B 转录，从而控制红细胞分化。
