''MN1'' is a

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

found on human

chromosome 22 Chromosome 22 is one of the 23 pairs of chromosomes in human cell (biology), cells. Humans normally have two copies of chromosome 22 in each cell. Chromosome 22 is the second smallest human chromosome, spanning about 49 million DNA base pairs and ...

, with gene map locus 22q12.3-qter. Its official full name is meningioma (disrupted in balanced translocation) 1 because it is disrupted by a

balanced translocation In genetics, chromosome translocation is a phenomenon that results in unusual rearrangement of chromosomes. This includes balanced and unbalanced translocation, with two main types: reciprocal-, and Robertsonian translocation. Reciprocal translo ...

(4;22) in a

meningioma Meningioma, also known as meningeal tumor, is typically a slow-growing tumor that forms from the meninges, the membranous layers surrounding the brain and spinal cord. Symptoms depend on the location and occur as a result of the tumor pressing o ...

Function

MN1 is a

transcription coregulator In molecular biology and genetics, transcription coregulators are proteins that interact with transcription factors to either activate or repress the transcription of specific genes. Transcription coregulators that activate gene transcription are ...

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 A coactivator is a type of transcriptional coregulator that binds to an activator (a transcription factor) to increase the rate of transcription of a gene or set of genes. The activator contains a DNA binding domain that binds either to a DNA p ...

of several transcription factors, including

RAR RAR or Rar may refer to: * Radio acoustic ranging, a non-visual technique for determining a ship's position at sea * "rar", the ISO 639-2 code for the Cook Islands Māori language * RAR (file format), a proprietary compressed archive file format in ...

/ RXR and the

vitamin D receptor The vitamin D receptor (VDR also known as the calcitriol receptor) is a member of the nuclear receptor family of transcription factors. Calcitriol (the active form of vitamin D, 1,25-(OH)2vitamin D3) binds to VDR, which then forms a heterodimer ...

. In AML, MN1 binds to genomic sites enriched for binding motifs of ETS factors as well as hematopoietic transcription factors such as

RUNX1 Runt-related transcription factor 1 (RUNX1) also known as acute myeloid leukemia 1 protein (AML1) or core-binding factor subunit alpha-2 (CBFA2) is a protein that in humans is encoded by the ''RUNX1'' gene. RUNX1 is a transcription factor that re ...

GATA2 GATA2 or GATA-binding factor 2 is a transcription factor, i.e. a nuclear protein which regulates the expression of genes. It regulates many genes that are critical for the embryonic development, self-renewal, maintenance, and functionality of b ...

, HOXA cluster genes, and

MEIS1 Homeobox protein Meis1 is a protein that in humans is encoded by the MEIS1 gene. Function Homeobox genes, of which the most well-characterized category is represented by the HOX genes, play a crucial role in normal development. In addition, se ...

. MN1 induces a hematopoietic stem and progenitor gene expression program centered on HOXA cluster genes, particularly

HOXA9 Homeobox protein Hox-A9 is a protein that in humans is encoded by the ''HOXA9'' gene. In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromoso ...

and

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 ETV6 (i.e. translocation-Ets-leukemia virus) protein is a transcription factor that in humans is encoded by the ''ETV6'' (previously known as ''TEL'') gene. The ETV6 protein regulates the development and growth of diverse cell types, particularly ...

STAT3 Signal transducer and activator of transcription 3 (STAT3) is a transcription factor which in humans is encoded by the ''STAT3'' gene. It is a member of the STAT protein family. Function STAT3 is a member of the STAT protein family. In respons ...

and

FLI1 Friend leukemia integration 1 transcription factor (FLI1), also known as transcription factor ERGB, is a protein that in humans is encoded by the ''FLI1'' gene, which is a proto-oncogene. Function Fli-1 is a member of the ETS transcription fa ...

. 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 Rhombencephalosynapsis is a rare genetic disorder, genetic brain abnormality of malformation of the cerebellum. The cerebellar vermis is either absent or only partially formed, and fusion is seen in varying degree between the cerebellar hemispheres ...

Function

Clinical significance

References

Further reading