Biology:MN1 (gene)
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Short description: Protein-coding gene in the species Homo sapiens
 Generic protein structure example |
MN1 is a gene found on human chromosome 22, with gene map locus 22q12.3-qter.[1] Its official full name is meningioma (disrupted in balanced translocation) 1 because it is disrupted by a balanced translocation (4;22) in a meningioma.
Function
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.[2] RAC3 and p300.[3] MN1 can act as a coactivator of several transcription factors, including RAR/RXR and the vitamin D receptor.[4] 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.[2] 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[5][2]
Clinical significance
The translocation of MN1 was first reported in meningioma.[1] A substantial percentage of primitive neuro-ectodermal tumors (PNET) have MN1 translocations[6] 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)[7] Described fusion partners include ETV6, STAT3 and FLI1.[8][7][9] About 50% of fusions are out of frame and result in high expression of MN1 via enhancer hijacking.[7][2] High MN1 expression in AML and MDS is associated with poor outcome [10][11][12][13][14][15][16][excessive citations]
Mutations in this gene have been associated with cleft palate[17][18][19] and an atypical form of rhombencephalosynapsis.[20]
References
- ↑ 1.0 1.1 "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. April 1995. PMID 7731706.
- ↑ 2.0 2.1 2.2 2.3 "Intrinsically disordered Meningioma-1 stabilizes the BAF complex to cause AML". Molecular Cell 81 (11): 2332–2348.e9. June 2021. doi:10.1016/j.molcel.2021.04.014. ISSN 1097-2765. PMID 33974912.
- ↑ "The MN1 oncoprotein synergizes with coactivators RAC3 and p300 in RAR-RXR-mediated transcription". Oncogene 22 (5): 699–709. February 2003. doi:10.1038/sj.onc.1206124. PMID 12569362.
- ↑ "The 1,25(OH)2D3-regulated transcription factor MN1 stimulates vitamin D receptor-mediated transcription and inhibits osteoblastic cell proliferation". Molecular Endocrinology 19 (9): 2234–44. September 2005. doi:10.1210/me.2005-0081. PMID 15890672.
- ↑ "Cell of origin in AML: susceptibility to MN1-induced transformation is regulated by the MEIS1/AbdB-like HOX protein complex". Cancer Cell 20 (1): 39–52. July 2011. doi:10.1016/j.ccr.2011.06.020. PMID 21741595.
- ↑ "New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs". Cell 164 (5): 1060–1072. February 2016. doi:10.1016/j.cell.2016.01.015. PMID 26919435.
- ↑ 7.0 7.1 7.2 "Ectopia associated MN1 fusions and aberrant activation in myeloid neoplasms with t(12;22)(p13;q12)". Cancer Gene Therapy 27 (10–11): 810–818. November 2020. doi:10.1038/s41417-019-0159-x. PMID 31902945.
- ↑ "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. April 1995. PMID 7731705.
- ↑ "AMKL chimeric transcription factors are potent inducers of leukemia". Leukemia 31 (10): 2228–2234. October 2017. doi:10.1038/leu.2017.51. PMID 28174417.
- ↑ "High meningioma 1 (MN1) expression as a predictor for poor outcome in acute myeloid leukemia with normal cytogenetics". Blood 108 (12): 3898–905. December 2006. doi:10.1182/blood-2006-04-014845. PMID 16912223.
- ↑ "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. March 2012. doi:10.1002/gcc.20950. PMID 22072540.
- ↑ "Prognostic importance of MN1 transcript levels, and biologic insights from MN1-associated gene and microRNA expression signatures in cytogenetically normal acute myeloid leukemia: a cancer and leukemia group B study". Journal of Clinical Oncology 27 (19): 3198–204. July 2009. doi:10.1200/JCO.2008.20.6110. PMID 19451432.
- ↑ "ERG expression is an independent prognostic factor and allows refined risk stratification in cytogenetically normal acute myeloid leukemia: a comprehensive analysis of ERG, MN1, and BAALC transcript levels using oligonucleotide microarrays". Journal of Clinical Oncology 27 (30): 5031–8. October 2009. doi:10.1200/JCO.2008.20.5328. PMID 19752345.
- ↑ "Low expression of MN1 associates with better treatment response in older patients with de novo cytogenetically normal acute myeloid leukemia". Blood 118 (15): 4188–98. October 2011. doi:10.1182/blood-2011-06-357764. PMID 21828125.
- ↑ "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. August 2013. doi:10.1007/s00277-013-1729-x. PMID 23515710.
- ↑ "MN1, a novel player in human AML". Blood Cells, Molecules & Diseases 39 (3): 336–9. 2007. doi:10.1016/j.bcmd.2007.06.009. PMID 17698380.
- ↑ "MN1 gene loss-of-function mutation causes cleft palate in a pedigree". Brain 144 (2): e18. March 2021. doi:10.1093/brain/awaa431. PMID 33351070.
- ↑ "Chromosome 22q12.1 microdeletions: confirmation of the MN1 gene as a candidate gene for cleft palate". European Journal of Human Genetics 24 (1): 51–8. January 2016. doi:10.1038/ejhg.2015.65. PMID 25944382.
- ↑ "Targeted disruption of the Mn1 oncogene results in severe defects in development of membranous bones of the cranial skeleton". Molecular and Cellular Biology 25 (10): 4229–36. May 2005. doi:10.1128/MCB.25.10.4229-4236.2005. PMID 15870292.
- ↑ "MN1 C-terminal truncation syndrome is a novel neurodevelopmental and craniofacial disorder with partial rhombencephalosynapsis". Brain 143 (1): 55–68. January 2020. doi:10.1093/brain/awz379. PMID 31834374.
Further reading
- "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. December 2005. doi:10.1182/blood-2005-04-1674. PMID 16081688.
- "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. June 2009. doi:10.1080/10428190902913591. PMID 19391034.
- "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. October 2008. doi:10.1093/carcin/bgn168. PMID 18632758.
- "MN1 overexpression is an important step in the development of inv(16) AML". Leukemia 21 (8): 1679–90. August 2007. doi:10.1038/sj.leu.2404778. PMID 17525718.
- "MN1 overexpression induces acute myeloid leukemia in mice and predicts ATRA resistance in patients with AML". Blood 110 (5): 1639–47. September 2007. doi:10.1182/blood-2007-03-080523. PMID 17494859.
- "Toward a confocal subcellular atlas of the human proteome". Molecular & Cellular Proteomics 7 (3): 499–508. March 2008. doi:10.1074/mcp.M700325-MCP200. PMID 18029348.
- "Conditional MN1-TEL knock-in mice develop acute myeloid leukemia in conjunction with overexpression of HOXA9". Blood 106 (13): 4269–77. December 2005. doi:10.1182/blood-2005-04-1679. PMID 16105979.
- "Reintroduction of CEBPA in MN1-overexpressing hematopoietic cells prevents their hyperproliferation and restores myeloid differentiation". Blood 114 (8): 1596–606. August 2009. doi:10.1182/blood-2009-02-205443. PMID 19561324.
- "Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling". Gut 58 (8): 1078–83. August 2009. doi:10.1136/gut.2008.169052. PMID 19240061. https://research.vumc.nl/en/publications/9f0b4115-baf6-4bc6-ab6b-4fd7f23f0f0a.
- "Development of a screening set for new (CAG/CTG)n dynamic mutations". Genomics 32 (1): 75–85. February 1996. doi:10.1006/geno.1996.0078. PMID 8786123.
- "A genome annotation-driven approach to cloning the human ORFeome". Genome Biology 5 (10): R84. 2004. doi:10.1186/gb-2004-5-10-r84. PMID 15461802.
- "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. August 2004. doi:10.1073/pnas.0404720101. PMID 15302935. Bibcode: 2004PNAS..10112130B.
- "The MN1 oncoprotein activates transcription of the IGFBP5 promoter through a CACCC-rich consensus sequence". Journal of Molecular Endocrinology 38 (1–2): 113–25. February 2007. doi:10.1677/jme.1.02110. PMID 17242174.
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