Growth factor independence 1 (GFI1) and the closely related protein GFI1B are small nuclear proteins that act as DNA binding transcriptional repressors. Both recognize the same consensus DNA binding motif via their C-terminal zinc finger domains and regulate the expression of their target genes by recruiting chromatin modifiers such as histone deacetylases (HDACs) and demethylases (LSD1) by using an N-terminal SNAG domain that comprises only 20 amino acids. The only region that is different between both proteins is the region that separates the zinc finger domains and the SNAG domain. Both proteins are co-expressed in hematopoietic stem cells (HSCs) and, to some extent, in multipotent progenitors (MPPs), but expression is specified as soon as early progenitors and show signs of lineage bias. While expression of GFI1 is maintained in lymphoid primed multipotent progenitors (LMPPs) that have the potential to differentiate into both myeloid and lymphoid cells, GFI1B expression is no longer detectable in these cells. By contrast, GFI1 expression is lost in megakaryocyte precursors (MKPs) and in megakaryocyte-erythrocyte progenitors (MEPs), which maintain a high level of GFI1B expression. Consequently, GFI1 drives myeloid and lymphoid differentiation and GFI1B drives the development of megakaryocytes, platelets, and erythrocytes. How such complementary cell type- and lineage-specific functions of GFI1 and GFI1B are maintained is still an unresolved question in particular since they share an almost identical structure and very similar biochemical modes of actions. The cell type-specific accessibility of GFI1/1B binding sites may explain the fact that very similar transcription factors can be responsible for very different transcriptional programming. An additional explanation comes from recent data showing that both proteins may have additional non-transcriptional functions. GFI1 interacts with a number of proteins involved in DNA repair and lack of GFI1 renders HSCs highly susceptible to DNA damage-induced death and restricts their proliferation. In contrast, GFI1B binds to proteins of the beta-catenin/Wnt signaling pathway and lack of GFI1B leads to an expansion of HSCs and MKPs, illustrating the different impact that GFI1 or GFI1B has on HSCs. In addition, GFI1 and GFI1B are required for endothelial cells to become the first blood cells during early murine development and are among those transcription factors needed to convert adult endothelial cells or fibroblasts into HSCs. This role of GFI1 and GFI1B bears high significance for the ongoing effort to generate hematopoietic stem and progenitor cells de novo for the autologous treatment of blood disorders such as leukemia and lymphoma.

生长因子独立性1（GFI1）和密切相关的蛋白质GFI1B是小的核蛋白，起着DNA结合转录阻遏物的作用。两者都识别相同的共有DNA结合基序通过通过使用仅包含20个氨基酸的N末端SNAG域，通过募集染色质修饰剂（例如组蛋白脱乙酰基酶（HDAC）和脱甲基酶（LSD1））来修饰它们的C末端锌指结构域，并调节其靶基因的表达。两种蛋白质之间唯一不同的区域是分隔锌指结构域和SNAG结构域的区域。两种蛋白在造血干细胞（HSC）中和某种程度上在多能祖细胞（MPPs）中共表达，但表达要在早期祖细胞中尽快表达，并显示出谱系偏向的迹象。虽然GFI1的表达在可能分化为髓样细胞和淋巴样细胞的淋巴致敏多能祖细胞（LMPPs）中得以维持，但在这些细胞中不再可检测到GFI1B表达。相比之下，GFI1表达在巨核细胞前体（MKP）和巨核细胞-红血球祖细胞（MEP）中丢失，它们保持了高水平的GFI1B表达。因此，GFI1驱动髓样和淋巴样分化，而GFI1B驱动巨核细胞，血小板和红细胞的发育。GFI1和GFI1B如何维持这种互补的细胞类型和谱系特异性功能仍然是一个尚未解决的问题，特别是因为它们具有几乎相同的结构和非常相似的生物化学作用方式。GFI1 / 1B结合位点的细胞类型特异性可及性可能解释了一个事实，即非常相似的转录因子可能导致非常不同的转录程序。来自最近的数据的另一个解释是，这两种蛋白都可能具有其他非转录功能。GFI1与许多参与DNA修复的蛋白质相互作用，缺乏GFI1使得HSC对DNA损伤诱导的死亡高度敏感，并限制了它们的增殖。相反，GFI1B与β-catenin/ Wnt信号通路的蛋白质结合，缺乏GFI1B导致HSC和MKP扩增，说明GFI1或GFI1B对HSC具有不同的影响。另外，GFI1和GFI1B是内皮细胞在早期鼠类发育过程中成为第一个血细胞所必需的，并且是将成人内皮细胞或成纤维细胞转化为HSC所需的那些转录因子之一。GFI1和GFI1B的这种作用对于正在进行的生成造血干细胞和祖细胞的工作具有高度意义。从头 自体治疗血液疾病，例如白血病和淋巴瘤。