This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Isono, K.-i.
Right arrow Articles by Koseki, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Isono, K.-i.
Right arrow Articles by Koseki, H.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, August 2005, p. 6694-6706, Vol. 25, No. 15
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.15.6694-6706.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Mammalian Polyhomeotic Homologues Phc2 and Phc1 Act in Synergy To Mediate Polycomb Repression of Hox Genes

Kyo-ichi Isono,1,2 Yu-ichi Fujimura,1,2 Jun Shinga,1,2 Makoto Yamaki,2 Jiyang O-Wang,1 Yoshihiro Takihara,3 Yasuaki Murahashi,1,2 Yuki Takada,1,2 Yoko Mizutani-Koseki,1,2 and Haruhiko Koseki1,2*

RIKEN Research Center for Allergy and Immunology, 1-7-22 Suehiro, Tsurumi-ku, Yokohama 230-0045, Japan,1 Department of Molecular Embryology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, China 260-8670, Japan,2 Department of Stem Cell Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan3

Received 2 December 2004/ Returned for modification 27 January 2005/ Accepted 4 May 2005

The Polycomb group (PcG) gene products form multimeric protein complexes and contribute to anterior-posterior (A-P) specification via the transcriptional regulation of Hox cluster genes. The Drosophila polyhomeotic genes and their mammalian orthologues, Phc1, Phc2, and Phc3, encode nuclear proteins that are constituents of evolutionarily conserved protein complexes designated class II PcG complexes. In this study, we describe the generation and phenotypes of Phc2-deficient mice. We show posterior transformations of the axial skeleton and premature senescence of mouse embryonic fibroblasts associated with derepression of Hox cluster genes and Cdkn2a genes, respectively. Synergistic actions of a Phc2 mutation with Phc1 and Rnf110 mutations during A-P specification, coimmunoprecipitation of their products from embryonic extracts, and chromatin immunoprecipitation by anti-Phc2 monoclonal antibodies suggest that Hox repression by Phc2 is mediated through the class II PcG complexes, probably via direct binding to the Hox locus. The genetic interactions further reveal the functional overlap between Phc2 and Phc1 and a strict dose-dependent requirement during A-P specification and embryonic survival. Functional redundancy between Phc2 and Phc1 leads us to hypothesize that the overall level of polyhomeotic orthologues in nuclei is a parameter that is critical in enabling the class II PcG complexes to exert their molecular functions.

* Corresponding author. Mailing address: RIKEN Research Center for Allergy and Immunology, 1-7-22 Suehiro, Tsurumi-ku, Yokohama 230-0045, Japan. Phone: 81-45-503-9689. Fax: 81-45-503-9688. E-mail: koseki{at}rcai.riken.jp.

Molecular and Cellular Biology, August 2005, p. 6694-6706, Vol. 25, No. 15
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.15.6694-6706.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Zamudio, N. M, Chong, S., O'Bryan, M. K (2008). Epigenetic regulation in male germ cells. Reproduction 136: 131-146 [Abstract] [Full Text]  
  • Ren, X., Vincenz, C., Kerppola, T. K. (2008). Changes in the Distributions and Dynamics of Polycomb Repressive Complexes during Embryonic Stem Cell Differentiation. Mol. Cell. Biol. 28: 2884-2895 [Abstract] [Full Text]  
  • Endoh, M., Endo, T. A., Endoh, T., Fujimura, Y.-i., Ohara, O., Toyoda, T., Otte, A. P., Okano, M., Brockdorff, N., Vidal, M., Koseki, H. (2008). Polycomb group proteins Ring1A/B are functionally linked to the core transcriptional regulatory circuitry to maintain ES cell identity. Development 135: 1513-1524 [Abstract] [Full Text]  
  • Miki, J., Fujimura, Y.-i., Koseki, H., Kamijo, T. (2007). Polycomb complexes regulate cellular senescence by repression of ARF in cooperation with E2F3.. GENES CELLS 12: 1371-1382 [Abstract] [Full Text]  
  • Xu, X., Bieda, M., Jin, V. X., Rabinovich, A., Oberley, M. J., Green, R., Farnham, P. J. (2007). A comprehensive ChIP chip analysis of E2F1, E2F4, and E2F6 in normal and tumor cells reveals interchangeable roles of E2F family members. Genome Res 17: 1550-1561 [Abstract] [Full Text]  
  • Takada, Y., Isono, K.-i., Shinga, J., Turner, J. M. A., Kitamura, H., Ohara, O., Watanabe, G., Singh, P. B., Kamijo, T., Jenuwein, T., Burgoyne, P. S., Koseki, H. (2007). Mammalian Polycomb Scmh1 mediates exclusion of Polycomb complexes from the XY body in the pachytene spermatocytes. Development 134: 579-590 [Abstract] [Full Text]  
  • Kotake, Y., Cao, R., Viatour, P., Sage, J., Zhang, Y., Xiong, Y. (2007). pRB family proteins are required for H3K27 trimethylation and Polycomb repression complexes binding to and silencing p16INK4a tumor suppressor gene. Genes Dev. 21: 49-54 [Abstract] [Full Text]  
  • Kim, S. Y., Paylor, S. W., Magnuson, T., Schumacher, A. (2006). Juxtaposed Polycomb complexes co-regulate vertebral identity. Development 133: 4957-4968 [Abstract] [Full Text]  
  • Fujimura, Y.-i., Isono, K.-i., Vidal, M., Endoh, M., Kajita, H., Mizutani-Koseki, Y., Takihara, Y., van Lohuizen, M., Otte, A., Jenuwein, T., Deschamps, J., Koseki, H. (2006). Distinct roles of Polycomb group gene products in transcriptionally repressed and active domains of Hoxb8. Development 133: 2371-2381 [Abstract] [Full Text]  
  • MASUI, O., HEARD, E. (2006). RNA and Protein Actors in X-Chromosome Inactivation. Cold Spring Harb Symp Quant Biol 71: 419-428 [Abstract]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»