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Nat Commun. 2017 Jun 26;8(1):36. doi: 10.1038/s41467-017-00052-2.

Flipping between Polycomb repressed and active transcriptional states introduces noise in gene expression.

Author information

1
European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, UK.
2
Department of New Biology, DGIST, Daegu, 42988, Republic of Korea.
3
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
4
Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Robert Roessle Strasse, Berlin-Buch, 13125, Germany.
5
Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3LY, UK.
6
Department of Genetics, Evolution and Environment, University College London, Gower Street, London, WC1E 6BT, UK.
7
William Harvey Research Institute, Queen Mary University London, Charterhouse Square, London, EC1M 6BQ, UK.
8
Nuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK.
9
Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK.
10
European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, UK. st9@sanger.ac.uk.
11
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK. st9@sanger.ac.uk.

Abstract

Polycomb repressive complexes (PRCs) are important histone modifiers, which silence gene expression; yet, there exists a subset of PRC-bound genes actively transcribed by RNA polymerase II (RNAPII). It is likely that the role of Polycomb repressive complex is to dampen expression of these PRC-active genes. However, it is unclear how this flipping between chromatin states alters the kinetics of transcription. Here, we integrate histone modifications and RNAPII states derived from bulk ChIP-seq data with single-cell RNA-sequencing data. We find that Polycomb repressive complex-active genes have greater cell-to-cell variation in expression than active genes, and these results are validated by knockout experiments. We also show that PRC-active genes are clustered on chromosomes in both two and three dimensions, and interactions with active enhancers promote a stabilization of gene expression noise. These findings provide new insights into how chromatin regulation modulates stochastic gene expression and transcriptional bursting, with implications for regulation of pluripotency and development.Polycomb repressive complexes modify histones but it is unclear how changes in chromatin states alter kinetics of transcription. Here, the authors use single-cell RNAseq and ChIPseq to find that actively transcribed genes with Polycomb marks have greater cell-to-cell variation in expression.

PMID:
28652613
PMCID:
PMC5484669
DOI:
10.1038/s41467-017-00052-2
[Indexed for MEDLINE]
Free PMC Article

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