Zinc finger protein Gfi-1 is a transcriptional repressor that in humans is encoded by the GFI1 gene. It is important normal hematopoiesis.
Function
Gfi1 (growth factor independence 1) is a transcriptional repressor that plays a critical role in hematopoiesis and in protecting hematopoietic cells against stress-induced apoptosis. Gfi1 upregulates the expression of the nuclear protein Hemgn, which contributes to its anti-apoptotic activity. This upregulation is mediated through a specific 16-bp promoter region and is dependent on Gfi1’s interaction with the histone demethylase LSD1. Gfi1 represses PU.1 transcription factor, and this repression precedes and correlates with the upregulation of Hemgn. The upregulation of Hemgn, in turn, contributes to the anti-apoptotic function of Gfi1, acting in a p53-independent manner.
Gfi1 promotes cell survival by upregulating Hemgn through the repression of PU.1 thereby inhibiting apoptosis. Gfi1 inhibits apoptosis induced by DNA damage, growth factor withdrawal, inhibitory cytokine TGF-β and MYC activation
Gfi1 is also expressed in the inner ear, and in the epithelium lining the stomach, intestines, and lung airways, where it is important for cellular differentiation.
In lymphoid lineages, GFI1 plays a vital role in directing cell fate decisions, differentiation and functional maintenance. Within CD8+ T cells, GFI1-driven transcriptional and epigenetic programs are essential for preserving cellular stemness and long-term persistence. Beyond the T cell lineage, the GFI1–FOXO1 axis functions as a key regulator of natural killer (NK) cell maturation and effector function.
