- Source: HEMGN
Hemogen is a protein that in humans is encoded by the HEMGN gene.
Hemgn Expression Regulation by Gfi1
Gfi1 (growth factor independence 1) is a transcriptional repressor involved in hematopoiesis, and it plays a crucial role in protecting hematopoietic cells from stress-induced apoptosis. The Hemgn gene is regulated by Gfi1 through a 16-bp promoter region, which is specifically located between +47 and +63 bp relative to the transcription start site (TSS). This regulation is dependent on Gfi1's interaction with the histone demethylase LSD1.
The key interaction mechanisms are as follows:
Gfi1 activates Hemgn expression through binding to its promoter region. Gfi1's activation is enhanced by its interaction with LSD1, which facilitates epigenetic modifications to increase the transcription of Hemgn.
Ikaros, another transcription factor, works synergistically with Gfi1 to further increase Hemgn expression. While Ikaros enhances Hemgn expression, it is not absolutely required for the Gfi1-mediated upregulation.
PU.1, another transcription factor, acts as a repressor of Hemgn. Gfi1 represses PU.1 expression, which precedes and correlates with the upregulation of Hemgn. In the absence of PU.1 (e.g., during knockdown or deficiency), Hemgn expression is augmented, showing that Gfi1 achieves Hemgn upregulation by suppressing PU.1.
The upregulation of Hemgn contributes significantly to the anti-apoptotic activity of Gfi1, allowing for cell survival under conditions of stress. This process occurs in a p53-independent manner, meaning that the anti-apoptotic effects of Gfi1 are not mediated through p53 pathways but rather through Hemgn regulation.
