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.

HEMGN
Identifiers
Aliases	HEMGN, CT155, EDAG, EDAG-1, NDR, hemogen
External IDs	OMIM: 610715; MGI: 2136910; HomoloGene: 14223; GeneCards: HEMGN; OMA:HEMGN - orthologs
Gene location (Human) Chr. Chromosome 9 (human) Band 9q22.33 Start 97,926,791 bp End 97,944,856 bp
Gene location (Mouse) Chr. Chromosome 4 (mouse) Band 4|4 B1 Start 46,393,989 bp End 46,413,506 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in trabecular bone sperm bone marrow bone marrow cells monocyte right testis left testis blood testicle ganglionic eminence Top expressed in fetal liver hematopoietic progenitor cell tibiofemoral joint human fetus body of femur spleen right lobe of liver blood bone marrow tail of embryo yolk sac More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding Cellular component nucleus nucleoplasm Biological process multicellular organism development cell differentiation regulation of osteoblast differentiation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 55363 93966 Ensembl ENSG00000136929 ENSMUSG00000028332 UniProt Q9BXL5 Q9ERZ0 RefSeq (mRNA) NM_018437 NM_197978 NM_053149 RefSeq (protein) NP_060907 NP_932095 NP_444379 Location (UCSC) Chr 9: 97.93 – 97.94 Mb Chr 4: 46.39 – 46.41 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

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.

Further reading

• Yang LV, Nicholson RH, Kaplan J, et al. (2001). "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. doi:10.1016/S0925-4773(01)00376-8. PMID 11404085. S2CID 2968450.
• Yu Y, Zhang C, Zhou G, et al. (2001). "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. doi:10.1101/gr.175501. PMC 311073. PMID 11483580.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "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. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Yang LV, Heng HH, Wan J, et al. (2004). "Alternative promoters and polyadenylation regulate tissue-specific expression of Hemogen isoforms during hematopoiesis and spermatogenesis". Dev. Dyn. 228 (4): 606–16. doi:10.1002/dvdy.10399. PMID 14648837. S2CID 26030697.
• Liu CC, Chou YL, Ch'ang LY (2004). "Down-regulation of human NDR gene in megakaryocytic differentiation of erythroleukemia K562 cells". J. Biomed. Sci. 11 (1): 104–16. doi:10.1159/000075293. PMID 14730214. S2CID 202650770.
• Humphray SJ, Oliver K, Hunt AR, et al. (2004). "DNA sequence and analysis of human chromosome 9". Nature. 429 (6990): 369–74. Bibcode:2004Natur.429..369H. doi:10.1038/nature02465. PMC 2734081. PMID 15164053.
• Li CY, Zhan YQ, Xu CW, et al. (2005). "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. doi:10.1038/sj.cdd.4401490. PMID 15332117.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• An LL, Li G, Wu KF, et al. (2005). "High expression of EDAG and its significance in AML". Leukemia. 19 (8): 1499–502. doi:10.1038/sj.leu.2403808. PMID 15920494. S2CID 5280303.
• Yang LV, Wan J, Ge Y, et al. (2006). "The GATA site-dependent hemogen promoter is transcriptionally regulated by GATA1 in hematopoietic and leukemia cells". Leukemia. 20 (3): 417–25. doi:10.1038/sj.leu.2404105. PMID 16437149. S2CID 9613437.
• Ling B, Zhou Y, Feng D, et al. (2007). "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. doi:10.3892/or.18.3.659. PMID 17671716.