Polycomb-group proteins

Polycomb-group proteins are a family of proteins first discovered in fruit flies that can remodel chromatin such that epigenetic silencing of genes takes place. Polycomb-group proteins are well known for silencing Hox genes through modulation of chromatin structure during embryonic development in fruit flies (Drosophila melanogaster).[1]

In insects

In Drosophila, the Trithorax-group (trxG) and Polycomb-group (PcG) proteins act antagonistically and interact with chromosomal elements, termed Cellular Memory Modules (CMMs). Trithorax-group (trxG) proteins maintain the active state of gene expression while the Polycomb-group (PcG) proteins counteract this activation with a repressive function that is stable over many cell generations and can only be overcome by germline differentiation processes. Polycomb Gene complexes or PcG silencing consist of at least three kinds of multiprotein complex Polycomb Repressive Complex 1 (PRC1), PRC2 and PhoRC. These complexes work together to carry out their repressive effect. PcGs proteins are evolutionarily conserved and exist in at least two separate protein complexes; the PcG repressive complex 1 (PRC1) and the PcG repressive complex 2–4 (PRC2/3/4). PRC2 catalyzes trimethylation of lysine 27 on histone H3 (H3K27me2/3), while PRC1 mono- ubiquitinates histone H2A on lysine 119 (H2AK119Ub1).

In mammals

In mammals Polycomb Group gene expression is important in many aspects of development like homeotic gene regulation and X chromosome inactivation, being recruited to the inactive X by Xist RNA, the master regulator of XCI.[2] The Bmi1 polycomb ring finger protein promotes neural stem cell self-renewal.[3][4] Murine null mutants in PRC2 genes are embryonic lethals while most PRC1 mutants are live born homeotic mutants that die perinatally. In contrast overexpression of PcG proteins correlates with the severity and invasiveness of several cancer types.[5] The mammalian PRC1 core complexes are very similar to Drosophila. Polycomb Bmi1 is known to regulate ink4 locus (p16Ink4a, p19Arf).[3][6]

The Polycomb gene FIE is expressed (blue) in unfertilised egg cells of the moss Physcomitrella patens (right) and expression ceases after fertilisation in the developing diploid sporophyte (left). In situ GUS staining of two female sex organs (archegonia) of a transgenic plant expressing a translational fusion of FIE-uidA under control of the native FIE promoter

In plants

In Physcomitrella patens the PcG protein FIE is specifically expressed in stem cells such as the unfertilized egg cell. Soon after fertilisation the FIE gene is inactivated in the young embryo.[7] The Polycomb gene FIE is expressed in unfertilised egg cells of the moss Physcomitrella patens and expression ceases after fertilisation in the developing diploid sporophyte.

It has been shown that unlike in mammals the PcG are necessary to keep the cells in a differentiated state. Consequently, loss of PcG causes de-differentiation and promotes embryonic development.[8]

Polycomb-group proteins also intervene in the control of flowering by silencing the Flowering Locus C gene.[9] This gene is a central part of the pathway that inhibits flowering in plants and its silencing during winter is suspected to be one of the main factors intervening in plant vernalization.[10]

See also

References

  1. ↑ Portoso M, Cavalli G (2008). "The Role of RNAi and Noncoding RNAs in Polycomb Mediated Control of Gene Expression and Genomic Programming". In Morris KV. RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity. Caister Academic Press. pp. 29–44. ISBN 978-1-904455-25-7.
  2. ↑ Ku M, Koche RP, Rheinbay E, Mendenhall EM, Endoh M, Mikkelsen TS, Presser A, Nusbaum C, Xie X, Chi AS, Adli M, Kasif S, Ptaszek LM, Cowan CA, Lander ES, Koseki H, Bernstein BE (2008). "Genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains". PLOS Genetics 4 (10): e1000242. doi:10.1371/journal.pgen.1000242. PMC: 2567431. PMID 18974828.
  3. 1 2 Molofsky AV, He S, Bydon M, Morrison SJ, Pardal R (2005). "Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and p19Arf senescence pathways". Genes & Development 19 (12): 1432–1437. doi:10.1101/gad.1299505. PMC: 1151659. PMID 15964994.
  4. ↑ Park IK, Morrison SJ, Clarke MF (2004). "Bmi1, stem cells, and senescence regulation". Journal of Clinical Investigation 113 (2): 175–179. doi:10.1172/JCI20800. PMC: 311443. PMID 14722607.
  5. ↑ Sauvageau M, Sauvageau G (April 2008). "Polycomb group genes: keeping stem cell activity in balance". PLoS Biol. 6 (4): e113. doi:10.1371/journal.pbio.0060113. PMC: 2689701. PMID 18447587.
  6. ↑ Popov N, Gil J (2010). "Epigenetic regulation of the INK4b-ARF-INK4a locus: in sickness and in health" (PDF). EPIGENETICS 5 (8): 685–690. doi:10.4161/epi.5.8.12996. PMC: 3052884. PMID 20716961.
  7. ↑ Mosquna A, Katz A, Decker EL, Rensing SA, Reski R, Ohad N (July 2009). "Regulation of stem cell maintenance by the Polyclmb protein FIE has been conserved during land plant evolution". Development 136 (14): 2433–44. doi:10.1242/dev.035048. PMID 19542356.
  8. ↑ Aichinger E, Villar CB, Farrona S, Reyes JC, Hennig L, Köhler C (August 2009). "CHD3 proteins and polycomb group proteins antagonistically determine cell identity in Arabidopsis". PLoS Genet. 5 (8): e1000605. doi:10.1371/journal.pgen.1000605. PMC: 2718830. PMID 19680533.
  9. ↑ Jiang D, Wang Y, Wang Y, He Y (2008). "Repression of FLOWERING LOCUS C and FLOWERING LOCUS T by the Arabidopsis Polycomb repressive complex 2 components". PLoS ONE 3 (10): e3404. doi:10.1371/journal.pone.0003404. PMC: 2561057. PMID 18852898.
  10. ↑ Sheldon CC, Rouse DT, Finnegan EJ, Peacock WJ, Dennis ES (March 2000). "The molecular basis of vernalization: the central role of FLOWERING LOCUS C (FLC)". Proc. Natl. Acad. Sci. U.S.A. 97 (7): 3753–8. doi:10.1073/pnas.060023597. PMC: 16312. PMID 10716723.

Further reading

  • Di Croce, L., & Helin, K. (2013) Transcriptional regulation by Polycomb group proteins. Nature structural & molecular biology, 20(10), 1147-1155. doi:10.1038/nsmb.2669
  • Jeffrey A. Simon, Robert E. Kingston (2013) Occupying Chromatin: Polycomb Mechanisms for Getting to Genomic Targets, Stopping Transcriptional Traffic, and Staying Put. Molecular Cell, 49(5), 808-824 doi:10.1016/j.molcel.2013.02.013
  • Shahram Golbabapour, Nazia Abdul Majid, Pouya Hassandarvish, Maryam Hajrezaie, Mahmood Ameen Abdulla, and A. Hamid A. Hadi. ( June 2013). Gene Silencing and Polycomb Group Proteins: An Overview of their Structure, Mechanisms and Phylogenetics. OMICS: A Journal of Integrative Biology, 17(6): 283-296. doi:10.1089/omi.2012.0105 free access
  • Schwartz YB, Pirrotta V (January 2007). "Polycomb silencing mechanisms and the management of genomic programmes". Nat. Rev. Genet. 8 (1): 9–22. doi:10.1038/nrg1981. PMID 17173055. 
  • Schuettengruber B, Chourrout D, Vervoort M, Leblanc B, Cavalli G (February 2007). "Genome regulation by polycomb and trithorax proteins". Cell 128 (4): 735–45. doi:10.1016/j.cell.2007.02.009. PMID 17320510. 

External links

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