Möröy Tarik, Vassen Lothar, Wilkes Brian, Khandanpour Cyrus
Institut de recherches cliniques de Montréal, Montréal, QC, Canada; Department de microbiologie, infectiologie et immunologie, Université de Montréal, Montréal, QC, Canada; Division of Experimental Medicine, McGill University, Montréal, QC, Canada; and.
Institut de recherches cliniques de Montréal, Montréal, QC, Canada; Department of Hematology, Universitätsklinikum Essen, Essen, Germany.
Blood. 2015 Dec 10;126(24):2561-9. doi: 10.1182/blood-2015-06-655043. Epub 2015 Oct 7.
The DNA-binding zinc finger transcription factors Gfi1 and Gfi1b were discovered more than 20 years ago and are recognized today as major regulators of both early hematopoiesis and hematopoietic stem cells. Both proteins function as transcriptional repressors by recruiting histone-modifying enzymes to promoters and enhancers of target genes. The establishment of Gfi1 and Gfi1b reporter mice made it possible to visualize their cell type-specific expression and to understand their function in hematopoietic lineages. We now know that Gfi1 is primarily important in myeloid and lymphoid differentiation, whereas Gfi1b is crucial for the generation of red blood cells and platelets. Several rare hematologic diseases are associated with acquired or inheritable mutations in the GFI1 and GFI1B genes. Certain patients with severe congenital neutropenia carry mutations in the GFI1 gene that lead to the disruption of the C-terminal zinc finger domains. Other mutations have been found in the GFI1B gene in families with inherited bleeding disorders. In addition, the Gfi1 locus is frequently found to be a proviral integration site in retrovirus-induced lymphomagenesis, and new, emerging data suggest a role of Gfi1 in human leukemia and lymphoma, underlining the role of both factors not only in normal hematopoiesis, but also in a wide spectrum of human blood diseases.
DNA 结合锌指转录因子 Gfi1 和 Gfi1b 在 20 多年前就被发现了，如今被公认为早期造血和造血干细胞的主要调节因子。这两种蛋白质都通过将组蛋白修饰酶招募到靶基因的启动子和增强子上来发挥转录抑制作用。Gfi1 和 Gfi1b 报告基因小鼠的建立使得可视化它们的细胞类型特异性表达并了解它们在造血谱系中的功能成为可能。我们现在知道，Gfi1 在髓系和淋巴系分化中起主要作用，而 Gfi1b 对红细胞和血小板的生成至关重要。几种罕见的血液疾病与 GFI1 和 GFI1B 基因的获得性或遗传性突变有关。某些严重先天性中性粒细胞减少症患者携带 GFI1 基因的突变，这些突变导致 C 末端锌指结构域的破坏。在患有遗传性出血性疾病的家族中，还发现了 GFI1B 基因的其他突变。此外，在逆转录病毒诱导的淋巴瘤发生过程中，经常发现 Gfi1 基因座是一个前病毒整合位点，新出现的数据表明 Gfi1 在人类白血病和淋巴瘤中发挥作用，这突出了这两种因子不仅在正常造血中，而且在广泛的人类血液疾病中的作用。
