HEMGN explained

Hemogen is a protein that in humans is encoded by the HEMGN gene.^[1] Hemgn Expression Regulation by Gfi1Gfi1 (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.^[2]

Further reading

• Yang LV, Nicholson RH, Kaplan J, etal . Hemogen is a novel nuclear factor specifically expressed in mouse hematopoietic development and its human homologue EDAG maps to chromosome 9q22, a region containing breakpoints of hematological neoplasms. . Mech. Dev. . 104 . 1–2 . 105–11 . 2001 . 11404085 . 10.1016/S0925-4773(01)00376-8 . 2968450 .
• Yu Y, Zhang C, Zhou G, etal . Gene expression profiling in human fetal liver and identification of tissue- and developmental-stage-specific genes through compiled expression profiles and efficient cloning of full-length cDNAs . Genome Res. . 11 . 8 . 1392–403 . 2001 . 11483580 . 10.1101/gr.175501 . 311073 .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Yang LV, Heng HH, Wan J, etal . Alternative promoters and polyadenylation regulate tissue-specific expression of Hemogen isoforms during hematopoiesis and spermatogenesis . Dev. Dyn. . 228 . 4 . 606–16 . 2004 . 14648837 . 10.1002/dvdy.10399 . 26030697 . free .
• Liu CC, Chou YL, Ch'ang LY . Down-regulation of human NDR gene in megakaryocytic differentiation of erythroleukemia K562 cells . J. Biomed. Sci. . 11 . 1 . 104–16 . 2004 . 14730214 . 10.1159/000075293 . 202650770 .
• Humphray SJ, Oliver K, Hunt AR, etal . DNA sequence and analysis of human chromosome 9 . Nature . 429 . 6990 . 369–74 . 2004 . 15164053 . 10.1038/nature02465 . 2734081 . 2004Natur.429..369H .
• Li CY, Zhan YQ, Xu CW, etal . EDAG regulates the proliferation and differentiation of hematopoietic cells and resists cell apoptosis through the activation of nuclear factor-kappa B . Cell Death Differ. . 11 . 12 . 1299–308 . 2005 . 15332117 . 10.1038/sj.cdd.4401490 . free .
• Gerhard DS, Wagner L, Feingold EA, etal . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• An LL, Li G, Wu KF, etal . High expression of EDAG and its significance in AML . Leukemia . 19 . 8 . 1499–502 . 2005 . 15920494 . 10.1038/sj.leu.2403808 . 5280303 .
• Yang LV, Wan J, Ge Y, etal . The GATA site-dependent hemogen promoter is transcriptionally regulated by GATA1 in hematopoietic and leukemia cells . Leukemia . 20 . 3 . 417–25 . 2006 . 16437149 . 10.1038/sj.leu.2404105 . 9613437 .
• Ling B, Zhou Y, Feng D, etal . Down-regulation of EDAG expression by retrovirus-mediated small interfering RNA inhibits the growth and IL-8 production of leukemia cells . Oncol. Rep. . 18 . 3 . 659–64 . 2007 . 17671716 . 10.3892/or.18.3.659. free .

Notes and References

1. Web site: Entrez Gene: HEMGN hemogen.
2. 10.1016/j.jbc.2024.107860. free . Upregulation of nuclear protein Hemgn by transcriptional repressor Gfi1 through repressing PU.1 contributes to the anti-apoptotic activity of Gfi1 . 2024 . Journal of Biological Chemistry . 300 . 11 . 39374784 . ((G C B)), Hoyt LJ, Dovat S, Dong F . 11550643 .