M33 (gene)

Last updated

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]

Contents

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).

Location of the M33 gene on chromosome 11. Chromosome 11.png
Location of the M33 gene on chromosome 11.

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]

Mutation

Katoh-Fukui et al. (1998) [5] [16]

References

  1. 1 2 3 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.
  2. 1 2 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.
  3. ↑ 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.
  4. ↑ 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.
  5. 1 2 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.
  6. ↑ "M33 (34): sc-136387" (PDF). Santa Cruz Biotechnology, Inc.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. 1 2 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 . hdl: 10261/56003 . PMID   19412891.
  15. ↑ 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.
  16. ↑ 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.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.