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

Gozde Kar, Jong Kyoung Kim, Aleksandra A. Kolodziejczyk, Kedar Nath Natarajan, Elena Torlai Triglia, Borbala Mifsud, Sarah Elderkin, John C. Marioni, Ana Pombo and Sarah A. Teichmann ()
Additional contact information
Gozde Kar: Wellcome Trust Genome Campus
Jong Kyoung Kim: Wellcome Trust Genome Campus
Aleksandra A. Kolodziejczyk: Wellcome Trust Genome Campus
Kedar Nath Natarajan: Wellcome Trust Genome Campus
Elena Torlai Triglia: Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine
Borbala Mifsud: Cancer Research UK London Research Institute
Sarah Elderkin: The Babraham Institute, Babraham Research Campus
John C. Marioni: Wellcome Trust Genome Campus
Ana Pombo: Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine
Sarah A. Teichmann: Wellcome Trust Genome Campus

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-00052-2

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