M33 (gene)
M33 is a gene.[1] It is a mammalian homologue of Drosophila Polycomb.[1] It localises to euchromatin within interphase nuclei, but it is enriched within the centromeric heterochromatin of metaphase chromosomes.[1] In mice, the official symbol of M33 gene styled Cbx2 and the official name chromobox 2 are maintained by the MGI. Also known as pc; MOD2. In human ortholog CBX2, synonyms CDCA6, M33, SRXY5 from orthology source HGNC. M33 was isolated by means of the structural similarity of its chromodomain.[2] It contains a region of homology shared by Xenopus and Drosophila in the fifth exon. [3] Polycomb genes in Drosophila mediate changes in higher-order chromatin structure to maintain the repressed state of developmentally regulated genes .[4][5] It may also involved in the campomelic syndrome and neoplastic disorders linked to allele loss in this region.[6] Disruption of the murine M33 gene, displayed posterior transformation of the sternal ribs and vertebral columns .[7]
Gene location
The mouse M33 gene is located on the Chromosome 11, from base pair 119,022,962 to base pair 119,031,270 (Build GRCm38/mm10). Human homolog of M33, Chromobox homolog 2 (CBX2 ) is located on Chromosome 17, from base pair 79,777,188 to base pair 79,787,650(Build GRCh38.p2).
![](../I/Chromosome_11.png.webp)
Protein structure
This protein contains Chromo (CHRromatin Organization MOdifier) domain and nuclear localization signal motif.[8] The full-length M33 sequence encodes a 519 amino acid (aa) protein.[2]
Function and mechanism
The mouse Polycomb group (PcG) protein M33 maintains repressed states of developmentally important genes, including homeotic genes and forms nuclear complexes with other PcG members. e.g.BMI1.[9] It also direct and/or indirect controls the vicinity of Hox genes regulatory regions, which are the accessibility of retinoic acid response elements .[10] homeotic transformations of the axial skeleton, and growth retardation.[11] [12] Moreover, the deficient of M33 also possessed abnormally few nucleated cells in the thymus and spleen, due to the aberrant T-cell expansion.[13] In transiently transfected cells, M33 acts as a transcriptional repressor . Biochemical assays indicate that two murine proteins, Ring1A[14] and Ring1B[14] interact directly with the repressor domain of M33 and that Ring1A can also behave as a transcriptional repressor.[15]
References
- Wang G, Horsley D, Ma A, Otte AP, Hutchings A, Butcher GW, Singh PB (1997). "M33, a mammalian homologue of Drosophila Polycomb localises to euchromatin within interphase nuclei but is enriched within the centromeric heterochromatin of metaphase chromosomes". Cytogenetics and Cell Genetics. 78 (1): 50–5. doi:10.1159/000134626. PMID 9345907.
- Pearce JJ, Singh PB, Gaunt SJ (April 1992). "The mouse has a Polycomb-like chromobox gene". Development. 114 (4): 921–9. doi:10.1242/dev.114.4.921. PMID 1352241.
- Reijnen, Marlene J.; Hamer, Karien M.; den Blaauwen, Jan L.; Lambrechts, Caro; Schoneveld, Ilse; van Driel, Roel; Otte, Arie P. (1995-09-01). "Polycomb and bmi-1 homologs are expressed in overlapping patterns in Xenopus embryos and are able to interact with each other". Mechanisms of Development. 53 (1): 35–46. doi:10.1016/0925-4773(95)00422-X. PMID 8555110.
- Orlando V, Paro R (December 1993). "Mapping Polycomb-repressed domains in the bithorax complex using in vivo formaldehyde cross-linked chromatin". Cell. 75 (6): 1187–98. doi:10.1016/0092-8674(93)90328-n. PMID 7903220. S2CID 12569811.
- Katoh-Fukui Y, Tsuchiya R, Shiroishi T, Nakahara Y, Hashimoto N, Noguchi K, Higashinakagawa T (June 1998). "Male-to-female sex reversal in M33 mutant mice". Nature. 393 (6686): 688–92. Bibcode:1998Natur.393..688K. doi:10.1038/31482. PMID 9641679. S2CID 4399183.
- "M33 (34): sc-136387" (PDF). Santa Cruz Biotechnology, Inc.
- Katoh-Fukui Y, Owaki A, Toyama Y, Kusaka M, Shinohara Y, Maekawa M, Toshimori K, Morohashi K (September 2005). "Mouse Polycomb M33 is required for splenic vascular and adrenal gland formation through regulating Ad4BP/SF1 expression". Blood. 106 (5): 1612–20. doi:10.1182/blood-2004-08-3367. PMID 15899914.
- Hirose S, Komoike Y, Higashinakagawa T (September 2006). "Identification of a nuclear localization signal in mouse polycomb protein, M33". Zoological Science. 23 (9): 785–91. doi:10.2108/zsj.23.785. PMID 17043400. S2CID 12948692.
- Hashimoto N, Brock HW, Nomura M, Kyba M, Hodgson J, Fujita Y, Takihara Y, Shimada K, Higashinakagawa T (April 1998). "RAE28, BMI1, and M33 are members of heterogeneous multimeric mammalian Polycomb group complexes". Biochemical and Biophysical Research Communications. 245 (2): 356–65. doi:10.1006/bbrc.1998.8438. PMID 9571155.
- Bel-Vialar S, Coré N, Terranova R, Goudot V, Boned A, Djabali M (August 2000). "Altered retinoic acid sensitivity and temporal expression of Hox genes in polycomb-M33-deficient mice". Developmental Biology. 224 (2): 238–49. doi:10.1006/dbio.2000.9791. PMID 10926763.
- Baumann C, De La Fuente R (2011-01-11). "Role of polycomb group protein cbx2/m33 in meiosis onset and maintenance of chromosome stability in the Mammalian germline". Genes. 2 (1): 59–80. doi:10.3390/genes2010059. PMC 3244348. PMID 22200029.
- Ono M, Harley VR (February 2013). "Disorders of sex development: new genes, new concepts". Nature Reviews. Endocrinology. 9 (2): 79–91. doi:10.1038/nrendo.2012.235. PMID 23296159. S2CID 1041738.
- Coré N, Bel S, Gaunt SJ, Aurrand-Lions M, Pearce J, Fisher A, Djabali M (February 1997). "Altered cellular proliferation and mesoderm patterning in Polycomb-M33-deficient mice". Development. 124 (3): 721–9. doi:10.1242/dev.124.3.721. PMID 9043087.
- Vidal M (2009-01-01). "Role of polycomb proteins Ring1A and Ring1B in the epigenetic regulation of gene expression". The International Journal of Developmental Biology. 53 (2–3): 355–70. doi:10.1387/ijdb.082690mv. PMID 19412891.
- Schoorlemmer J, Marcos-Gutiérrez C, Were F, Martínez R, García E, Satijn DP, Otte AP, Vidal M (October 1997). "Ring1A is a transcriptional repressor that interacts with the Polycomb-M33 protein and is expressed at rhombomere boundaries in the mouse hindbrain". The EMBO Journal. 16 (19): 5930–42. doi:10.1093/emboj/16.19.5930. PMC 1170224. PMID 9312051.
- Biason-Lauber A, Konrad D, Meyer M, DeBeaufort C, Schoenle EJ (May 2009). "Ovaries and female phenotype in a girl with 46,XY karyotype and mutations in the CBX2 gene". American Journal of Human Genetics. 84 (5): 658–63. doi:10.1016/j.ajhg.2009.03.016. PMC 2680992. PMID 19361780.