rest–mediated recruitment of polycomb repressor complexes in mammalian cellsrest-mediated招聘polycomb抑制因子复合物在哺乳动物细胞.pdfVIP

REST–Mediated Recruitment of Polycomb Repressor Complexes in Mammalian Cells 1. 1. 1 1 2 2 Nikolaj Dietrich , Mads Lerdrup , Eskild Landt , Shuchi Agrawal-Singh , Mads Bak , Niels Tommerup , 3 ¨ 1 1 Juri Rappsilber , Erik Sodersten , Klaus Hansen * 1 Biotech Research and Innovation Centre (BRIC) and Centre for Epigenetics, University of Copenhagen, Copenhagen, Denmark, 2 Wilhelm Johannsen Centre For Functional Genome Research, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark, 3 Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom Abstract Polycomb Repressive Complex (PRC) 1 and PRC2 regulate genes involved in differentiation and development. However, the mechanism for how PRC1 and PRC2 are recruited to genes in mammalian cells is unclear. Here we present evidence for an interaction between the transcription factor REST, PRC1, and PRC2 and show that RNF2 and REST co-regulate a number of neuronal genes in human teratocarcinoma cells (NT2-D1). Using NT2-D1 cells as a model of neuronal differentiation, we furthermore showed that retinoic-acid stimulation led to displacement of PRC1 at REST binding sites, reduced H3K27Me3, and increased gene expression. Genome-wide analysis of Polycomb binding in Rest 2/ 2 and Eed 2/ 2 mouse embryonic stem (mES) cells showed that Rest was required for PRC1 recruitment to a subset of Polycomb regulated neuronal genes. Furthermore, we found that PRC1 can be recruited to Rest binding sites independently of CpG islands and the H3K27Me3 mark. Surprisingly, PRC2 was fr