MN1 is a gene found on human chromosome 22, with gene map locus 22q12.3-qter.[5] Its official full name is meningioma (disrupted in balanced translocation) 1 because it is disrupted by a balanced translocation (4;22) in a meningioma.
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MN1 is a transcription coregulator that enhances or represses gene expression through direct or indirect interaction with the gene regulatory machinery. Reported interactions include the BAF (SWI/SNF) complex.[6] RAC3 and p300.[7] MN1 can act as a coactivator of several transcription factors, including RAR/RXR and the vitamin D receptor.[8] In AML, MN1 binds to genomic sites enriched for binding motifs of ETS factors as well as hematopoietic transcription factors such as RUNX1, GATA2, HOXA cluster genes, and MEIS1.[6] MN1 induces a hematopoietic stem and progenitor gene expression program centered on HOXA cluster genes, particularly HOXA9 and MEIS1 via its interaction with the BAF complex[9][6]
The translocation of MN1 was first reported in meningioma.[5] A substantial percentage of primitive neuro-ectodermal tumors (PNET) have MN1 translocations[10] Several different partners were described, although in many cases no fusion partner was identified. MN1 transloations also occur in up to 2% of acute myeloid leukemia (AML)[11] Described fusion partners include ETV6, STAT3 and FLI1.[12][11][13] About 50% of fusions are out of frame and result in high expression of MN1 via enhancer hijacking.[11][6]
High MN1 expression in AML and MDS is associated with poor outcome [14][15][16][17][18][19][20][excessive citations]
Mutations in this gene have been associated with cleft palate[21][22][23] and an atypical form of rhombencephalosynapsis.[24]
Lekanne Deprez RH, Riegman PH, Groen NA, Warringa UL, van Biezen NA, Molijn AC, et al. (April 1995). "Cloning and characterization of MN1, a gene from chromosome 22q11, which is disrupted by a balanced translocation in a meningioma". Oncogene. 10 (8): 1521–8. PMID 7731706.
Buijs A, Sherr S, van Baal S, van Bezouw S, van der Plas D, Geurts van Kessel A, et al. (April 1995). "Translocation (12;22) (p13;q11) in myeloproliferative disorders results in fusion of the ETS-like TEL gene on 12p13 to the MN1 gene on 22q11". Oncogene. 10 (8): 1511–9. PMID 7731705.
Heuser M, Beutel G, Krauter J, Döhner K, von Neuhoff N, Schlegelberger B, Ganser A (December 2006). "High meningioma 1 (MN1) expression as a predictor for poor outcome in acute myeloid leukemia with normal cytogenetics". Blood. 108 (12): 3898–905. doi:10.1182/blood-2006-04-014845. PMID 16912223. S2CID 16434975.
Haferlach C, Kern W, Schindela S, Kohlmann A, Alpermann T, Schnittger S, Haferlach T (March 2012). "Gene expression of BAALC, CDKN1B, ERG, and MN1 adds independent prognostic information to cytogenetics and molecular mutations in adult acute myeloid leukemia". Genes, Chromosomes & Cancer. 51 (3): 257–65. doi:10.1002/gcc.20950. PMID 22072540. S2CID 205828447.
Xiang L, Li M, Liu Y, Cen J, Chen Z, Zhen X, et al. (August 2013). "The clinical characteristics and prognostic significance of MN1 gene and MN1-associated microRNA expression in adult patients with de novo acute myeloid leukemia". Annals of Hematology. 92 (8): 1063–9. doi:10.1007/s00277-013-1729-x. PMID 23515710. S2CID 23939296.
- Kawagoe H, Grosveld GC (December 2005). "MN1-TEL myeloid oncoprotein expressed in multipotent progenitors perturbs both myeloid and lymphoid growth and causes T-lymphoid tumors in mice". Blood. 106 (13): 4278–86. doi:10.1182/blood-2005-04-1674. PMC 1895241. PMID 16081688.
- Schroeder T, Czibere A, Zohren F, Aivado M, Gattermann N, Germing U, Haas R (June 2009). "Meningioma 1 gene is differentially expressed in CD34 positive cells from bone marrow of patients with myelodysplastic syndromes with the highest expression in refractory anemia with excess of blasts and secondary acute myeloid leukemia". Leukemia & Lymphoma. 50 (6): 1043–6. doi:10.1080/10428190902913591. PMID 19391034. S2CID 38372641.
- Meester-Smoor MA, Janssen MJ, Grosveld GC, de Klein A, van IJcken WF, Douben H, Zwarthoff EC (October 2008). "MN1 affects expression of genes involved in hematopoiesis and can enhance as well as inhibit RAR/RXR-induced gene expression". Carcinogenesis. 29 (10): 2025–34. doi:10.1093/carcin/bgn168. PMC 3202306. PMID 18632758.
- Carella C, Bonten J, Sirma S, Kranenburg TA, Terranova S, Klein-Geltink R, et al. (August 2007). "MN1 overexpression is an important step in the development of inv(16) AML". Leukemia. 21 (8): 1679–90. doi:10.1038/sj.leu.2404778. PMID 17525718. S2CID 21088872.
- Heuser M, Argiropoulos B, Kuchenbauer F, Yung E, Piper J, Fung S, et al. (September 2007). "MN1 overexpression induces acute myeloid leukemia in mice and predicts ATRA resistance in patients with AML". Blood. 110 (5): 1639–47. doi:10.1182/blood-2007-03-080523. PMID 17494859.
- Barbe L, Lundberg E, Oksvold P, Stenius A, Lewin E, Björling E, et al. (March 2008). "Toward a confocal subcellular atlas of the human proteome". Molecular & Cellular Proteomics. 7 (3): 499–508. doi:10.1074/mcp.M700325-MCP200. PMID 18029348.
- Kawagoe H, Grosveld GC (December 2005). "Conditional MN1-TEL knock-in mice develop acute myeloid leukemia in conjunction with overexpression of HOXA9". Blood. 106 (13): 4269–77. doi:10.1182/blood-2005-04-1679. PMC 1895240. PMID 16105979.
- Kandilci A, Grosveld GC (August 2009). "Reintroduction of CEBPA in MN1-overexpressing hematopoietic cells prevents their hyperproliferation and restores myeloid differentiation". Blood. 114 (8): 1596–606. doi:10.1182/blood-2009-02-205443. PMC 2731639. PMID 19561324.
- Trynka G, Zhernakova A, Romanos J, Franke L, Hunt KA, Turner G, et al. (August 2009). "Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling". Gut. 58 (8): 1078–83. doi:10.1136/gut.2008.169052. PMID 19240061. S2CID 17111427.
- Gastier JM, Brody T, Pulido JC, Businga T, Sunden S, Hu X, et al. (February 1996). "Development of a screening set for new (CAG/CTG)n dynamic mutations". Genomics. 32 (1): 75–85. doi:10.1006/geno.1996.0078. PMID 8786123.
- Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, et al. (2004). "A genome annotation-driven approach to cloning the human ORFeome". Genome Biology. 5 (10): R84. doi:10.1186/gb-2004-5-10-r84. PMC 545604. PMID 15461802.
- Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, et al. (August 2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proceedings of the National Academy of Sciences of the United States of America. 101 (33): 12130–5. Bibcode:2004PNAS..10112130B. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
- Meester-Smoor MA, Molijn AC, Zhao Y, Groen NA, Groffen CA, Boogaard M, et al. (February 2007). "The MN1 oncoprotein activates transcription of the IGFBP5 promoter through a CACCC-rich consensus sequence". Journal of Molecular Endocrinology. 38 (1–2): 113–25. doi:10.1677/jme.1.02110. PMID 17242174.