MN1 (gene)

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. RAC3 and p300. MN1 can act as a coactivator of several transcription factors, including RAR/RXR and the vitamin D receptor. 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. 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

Clinical significance

The translocation of MN1 was first reported in meningioma. A substantial percentage of primitive neuro-ectodermal tumors (PNET) have MN1 translocations 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) Described fusion partners include ETV6, STAT3 and FLI1. About 50% of fusions are out of frame and result in high expression of MN1 via enhancer hijacking. High MN1 expression in AML and MDS is associated with poor outcome

Mutations in this gene have been associated with cleft palate and an atypical form of rhombencephalosynapsis.

References

References

1. (April 1995). "Cloning and characterization of MN1, a gene from chromosome 22q11, which is disrupted by a balanced translocation in a meningioma". Oncogene.
2. (June 2021). "Intrinsically disordered Meningioma-1 stabilizes the BAF complex to cause AML". Molecular Cell.
3. (February 2003). "The MN1 oncoprotein synergizes with coactivators RAC3 and p300 in RAR-RXR-mediated transcription". Oncogene.
4. (September 2005). "The 1,25(OH)2D3-regulated transcription factor MN1 stimulates vitamin D receptor-mediated transcription and inhibits osteoblastic cell proliferation". Molecular Endocrinology.
5. (July 2011). "Cell of origin in AML: susceptibility to MN1-induced transformation is regulated by the MEIS1/AbdB-like HOX protein complex". Cancer Cell.
6. (February 2016). "New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs". Cell.
7. (November 2020). "Ectopia associated MN1 fusions and aberrant activation in myeloid neoplasms with t(12;22)(p13;q12)". Cancer Gene Therapy.
8. (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.
9. (October 2017). "AMKL chimeric transcription factors are potent inducers of leukemia". Leukemia.
10. (December 2006). "High meningioma 1 (MN1) expression as a predictor for poor outcome in acute myeloid leukemia with normal cytogenetics". Blood.
11. (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.
12. (July 2009). "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.
13. (October 2009). "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.
14. (October 2011). "Low expression of MN1 associates with better treatment response in older patients with de novo cytogenetically normal acute myeloid leukemia". Blood.
15. (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.
16. (2007). "MN1, a novel player in human AML". Blood Cells, Molecules & Diseases.
17. (March 2021). "MN1 gene loss-of-function mutation causes cleft palate in a pedigree". Brain.
18. (January 2016). "Chromosome 22q12.1 microdeletions: confirmation of the MN1 gene as a candidate gene for cleft palate". European Journal of Human Genetics.
19. (May 2005). "Targeted disruption of the Mn1 oncogene results in severe defects in development of membranous bones of the cranial skeleton". Molecular and Cellular Biology.
20. (January 2020). "MN1 C-terminal truncation syndrome is a novel neurodevelopmental and craniofacial disorder with partial rhombencephalosynapsis". Brain.