HEMGN

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) [1] Band 9q22.33 Start 97,926,791 bp [1] End 97,944,856 bp [1]
Gene location (Mouse) Chr. Chromosome 4 (mouse) [2] Band 4|4 B1 Start 46,393,989 bp [2] End 46,413,506 bp [2]
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 [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Hemogen is a protein that in humans is encoded by the HEMGN gene. ^[5]

Hemgn, a gene with anti-apoptotic properties, is a key downstream target of GFI1 (growth factor independence 1), a transcriptional repressor involved in hematopoiesis. GFI1 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 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. GFI1 activates Hemgn expression through promoter binding, and this activation is enhanced by LSD1-mediated epigenetic modifications that promote transcription of Hemgn.

Hemgn expression is further increased through the synergistic action of Ikaros, another transcription factor. ^[6] Although Ikaros enhances Hemgn expression, it is not strictly required for GFI1-mediated upregulation. ^[7] Together, GFI1 and Ikaros cooperate to maximize transcriptional activation of Hemgn.

Hemgn is negatively regulated by PU.1, a transcription factor that functions as a repressor of its expression. ^[8] GFI1 represses PU.1 expression, ^[9] leading to derepression and subsequent upregulation of Hemgn. In the absence of PU.1, such as in knockdown or deficiency models, Hemgn expression is enhanced, demonstrating that GFI1 promotes Hemgn expression indirectly by inhibiting PU.1.

Hemgn upregulation contributes significantly to the anti-apoptotic function of GFI1, enabling hematopoietic cells to survive under stress conditions. This protective effect is independent of the p53 pathway and instead relies specifically on Hemgn-mediated mechanisms. ^[7]

References

1. GRCh38: Ensembl release 89: ENSG00000136929 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000028332 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: HEMGN hemogen".
6. Olsson L, Johansson B (May 2015). "Ikaros and leukaemia". British Journal of Haematology. 169 (4): 479–491. doi:10.1111/bjh.13342. PMID   25753742.
7. Binod GC, Hoyt LJ, Dovat S, Dong F (November 2024). "Upregulation of nuclear protein Hemgn by transcriptional repressor GFI1 through repressing PU.1 contributes to the anti-apoptotic activity of GFI1". The Journal of Biological Chemistry. 300 (11) 107860. Bibcode:2024JBiCh.300j7860G. doi: 10.1016/j.jbc.2024.107860 . PMC   11550643 . PMID   39374784.
8. Kastner P, Chan S (2008). "PU.1: a crucial and versatile player in hematopoiesis and leukemia". The International Journal of Biochemistry & Cell Biology. 40 (1): 22–27. doi:10.1016/j.biocel.2007.01.026. PMID   17374502.
9. Dahl R, Iyer SR, Owens KS, Cuylear DD, Simon MC (March 2007). "The transcriptional repressor GFI-1 antagonizes PU.1 activity through protein-protein interaction". The Journal of Biological Chemistry. 282 (9): 6473–6483. doi: 10.1074/jbc.M607613200 . PMC   3218793 . PMID   17197705.

Further reading

• Yang LV, Nicholson RH, Kaplan J, Galy A, Li L (June 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". Mechanisms of Development. 104 (1–2): 105–111. doi:10.1016/S0925-4773(01)00376-8. PMID   11404085. S2CID   2968450.
• Yu Y, Zhang C, Zhou G, Wu S, Qu X, Wei H, et al. (August 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 Research. 11 (8): 1392–1403. doi:10.1101/gr.175501. PMC   311073 . PMID   11483580.
• Yang LV, Heng HH, Wan J, Southwood CM, Gow A, Li L (December 2003). "Alternative promoters and polyadenylation regulate tissue-specific expression of Hemogen isoforms during hematopoiesis and spermatogenesis". Developmental Dynamics. 228 (4): 606–616. 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". Journal of Biomedical Science. 11 (1): 104–116. doi:10.1159/000075293. PMID   14730214. S2CID   202650770.
• Li CY, Zhan YQ, Xu CW, Xu WX, Wang SY, Lv J, et al. (December 2004). "EDAG regulates the proliferation and differentiation of hematopoietic cells and resists cell apoptosis through the activation of nuclear factor-kappa B". Cell Death and Differentiation. 11 (12): 1299–1308. doi: 10.1038/sj.cdd.4401490 . PMID   15332117.
• An LL, Li G, Wu KF, Ma XT, Zheng GG, Qiu LG, et al. (August 2005). "High expression of EDAG and its significance in AML". Leukemia. 19 (8): 1499–1502. doi:10.1038/sj.leu.2403808. PMID   15920494. S2CID   5280303.
• Yang LV, Wan J, Ge Y, Fu Z, Kim SY, Fujiwara Y, et al. (March 2006). "The GATA site-dependent hemogen promoter is transcriptionally regulated by GATA1 in hematopoietic and leukemia cells". Leukemia. 20 (3): 417–425. doi:10.1038/sj.leu.2404105. PMID   16437149. S2CID   9613437.
• Ling B, Zhou Y, Feng D, Shen G, Gao T, Shi Y, et al. (September 2007). "Down-regulation of EDAG expression by retrovirus-mediated small interfering RNA inhibits the growth and IL-8 production of leukemia cells". Oncology Reports. 18 (3): 659–664. doi:10.3892/or.18.3.659. PMID   17671716.