Email updates

Keep up to date with the latest news and content from Genome Biology and BioMed Central.

Open Access Research

Genome-wide co-localization of Polycomb orthologs and their effects on gene expression in human fibroblasts

Helen Pemberton14, Emma Anderton15, Harshil Patel2, Sharon Brookes1, Hollie Chandler1, Richard Palermo1, Julie Stock15, Marc Rodriguez-Niedenführ16, Tomas Racek17, Lucas de Breed18, Aengus Stewart2, Nik Matthews3 and Gordon Peters1*

Author Affiliations

1 Molecular Oncology Laboratory, CRUK London Research Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK

2 Bioinformatics and Biostatistics Service, CRUK London Research Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK

3 Advanced Sequencing Facility, CRUK London Research Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK

4 Present address: Gene Function Laboratory, Breakthrough Breast Cancer, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK

5 Present address: Cancer Research Technology, Wolfson Institute for Biomedical Research, The Cruciform Building, Gower Street, London WC1E 6BT, UK

6 Present address: Departamento de Anatomía y Embriología Humana I, Complutense University of Madrid, Madrid, Spain

7 Present address: Dr von Haunersches Kinderspital, Lindwurmstr 2a, 80337, Munich, Germany

8 Present address: Graduate School of Business, Stanford University, Stanford, CA 94305-7298, USA

For all author emails, please log on.

Genome Biology 2014, 15:R23  doi:10.1186/gb-2014-15-2-r23

Published: 3 February 2014

Abstract

Background

Polycomb group proteins form multicomponent complexes that are important for establishing lineage-specific patterns of gene expression. Mammalian cells encode multiple permutations of the prototypic Polycomb repressive complex 1 (PRC1) with little evidence for functional specialization. An aim of this study is to determine whether the multiple orthologs that are co-expressed in human fibroblasts act on different target genes and whether their genomic location changes during cellular senescence.

Results

Deep sequencing of chromatin immunoprecipitated with antibodies against CBX6, CBX7, CBX8, RING1 and RING2 reveals that the orthologs co-localize at multiple sites. PCR-based validation at representative loci suggests that a further six PRC1 proteins have similar binding patterns. Importantly, sequential chromatin immunoprecipitation with antibodies against different orthologs implies that multiple variants of PRC1 associate with the same DNA. At many loci, the binding profiles have a distinctive architecture that is preserved in two different types of fibroblast. Conversely, there are several hundred loci at which PRC1 binding is cell type-specific and, contrary to expectations, the presence of PRC1 does not necessarily equate with transcriptional silencing. Interestingly, the PRC1 binding profiles are preserved in senescent cells despite changes in gene expression.

Conclusions

The multiple permutations of PRC1 in human fibroblasts congregate at common rather than specific sites in the genome and with overlapping but distinctive binding profiles in different fibroblasts. The data imply that the effects of PRC1 complexes on gene expression are more subtle than simply repressing the loci at which they bind.