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Development 129, 4171-4183 (2002)
© 2002 The Company of Biologists Limited

Involvement of the Polycomb-group gene Ring1B in the specification of the anterior-posterior axis in mice

Maki Suzuki1,2,*, Yoko Mizutani-Koseki1,*, Yu-ichi Fujimura1,*, Hiro Miyagishima1, Tomomi Kaneko1, Yuki Takada1, Takeshi Akasaka1, Hideki Tanzawa2, Yoshihiro Takihara3, Megumi Nakano4, Hiroshi Masumoto4, Miguel Vidal5, Kyo-ichi Isono1 and Haruhiko Koseki1,6,{dagger}

1 Department of Molecular Embryology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
2 Department of Oral Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan
3 Department of Develomental Biology and Medicine, Osaka Medical Center for Cancer and Cardiovascular Diseases, Nakamiti 1-3-3, Tousei-ku, Osaka, 537-8511, Japan
4 Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8602 Japan
5 Centro de Investigaciones Biologicas, Department of Developmental and Cell Biology, Velazquez 144, 28006 Madrid, Spain
6 RIKEN Research Center for Allergy and Immunology, 1-7-22 Suehiro, Tsurumi-ku, Yokohama 230-0045, Japan
* These authors contributed equally to this work

{dagger}Author for correspondence (e-mail: koseki{at}med.m.chiba-u.ac.jp)

Accepted 11 June 2002

The products of the Polycomb group of genes form complexes that maintain the state of transcriptional repression of several genes with relevance to development and in cell proliferation. We have identified Ring1B, the product of the Ring1B gene (Rnf2 – Mouse Genome Informatics), by means of its interaction with the Polycomb group protein Mel18. We describe biochemical and genetic studies directed to understand the biological role of Ring1B. Immunoprecipitation studies indicate that Ring1B form part of protein complexes containing the products of other Polycomb group genes, such as Rae28/Mph1 and M33, and that this complexes associate to chromosomal DNA. We have generated a mouse line bearing a hypomorphic Ring1B allele, which shows posterior homeotic transformations of the axial skeleton and a mild derepression of some Hox genes (Hoxb4, Hoxb6 and Hoxb8) in cells anterior to their normal boundaries of expression in the mesodermal compartment. By contrast, the overexpression of Ring1B in chick embryos results in the repression of Hoxb9 expression in the neural tube. These results, together with the genetic interactions observed in compound Ring1B/Mel18 mutant mice, are consistent with a role for Ring1B in the regulation of Hox gene expression by Polycomb group complexes.

Key words: Polycomb, Ring1B, Mel18, Hox, Mouse






© The Company of Biologists Ltd 2002