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First published online 13 March 2008
doi: 10.1242/dev.014340

Development 135, 1513-1524 (2008)
Published by The Company of Biologists 2008
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Polycomb group proteins Ring1A/B are functionally linked to the core transcriptional regulatory circuitry to maintain ES cell identity

Mitsuhiro Endoh1, Takaho A. Endo2, Tamie Endoh1, Yu-ichi Fujimura1, Osamu Ohara1, Tetsuro Toyoda2, Arie P. Otte3, Masaki Okano4, Neil Brockdorff5, Miguel Vidal1,6 and Haruhiko Koseki1,*

1 RIKEN Research Center for Allergy and Immunology, 1-7-22 Suehiro, Tsurumi-ku, Yokohama 230-0045, Japan.
2 RIKEN Genomic Sciences Center, 1-7-22 Suehiro, Tsurumi-ku, Yokohama 230-0045, Japan.
3 Swammerdam Institute for Life Sciences, University of Amsterdam, Kruislaan 406, 1098 SM Amsterdam, The Netherlands.
4 RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 6500047, Japan.
5 Developmental Epigenetics Group, MRC Clinical Sciences Centre, ICFM, Hammersmith Hospital, DuCane Road, London W12 ONN, UK.
6 Centro de Investigaciones Biologicas, Department of Developmental and Cell Biology, Ramiro de Maeztu 9, 28040 Madrid, Spain.

* Author for correspondence (e-mail: koseki{at}rcai.riken.jp)

Accepted 29 January 2008

The Polycomb group (PcG) proteins mediate heritable silencing of developmental regulators in metazoans, participating in one of two distinct multimeric protein complexes, the Polycomb repressive complexes 1 (PRC1) and 2 (PRC2). Although PRC2 has been shown to share target genes with the core transcription network, including Oct3/4, to maintain embryonic stem (ES) cells, it is still unclear whether PcG proteins and the core transcription network are functionally linked. Here, we identify an essential role for the core PRC1 components Ring1A/B in repressing developmental regulators in mouse ES cells and, thereby, in maintaining ES cell identity. A significant proportion of the PRC1 target genes are also repressed by Oct3/4. We demonstrate that engagement of PRC1 at target genes is Oct3/4-dependent, whereas engagement of Oct3/4 is PRC1-independent. Moreover, upon differentiation induced by Gata6 expression, most of the Ring1A/B target genes are derepressed and the binding of Ring1A/B to their target loci is also decreased. Collectively, these results indicate that Ring1A/B-mediated Polycomb silencing functions downstream of the core transcriptional regulatory circuitry to maintain ES cell identity.

Key words: Polycomb, Oct3/4 (Pou5f1), Gata6, ES cells, Chromatin, Silencing, Ring1A/B (Ring1/Rnf2), Mouse


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