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

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Item Type:

Article

Title:

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

Creators Name:

Kar, G. and Kim, J.K. and Kolodziejczyk, A.A. and Natarajan, K.N. and Torlai Triglia, E. and Mifsud, B. and Elderkin, S. and Marioni, J.C. and Pombo, A. and Teichmann, S.A.

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 PRC is to dampen expression of these PRC-active genes. However, it is unclear how this flipping between chromatin states alters the kinetics of transcriptional burst size and frequency relative to genes with exclusively activating marks. To investigate this, we integrate histone modifications and RNAPII states derived from bulk ChIP-seq data with single-cell RNA-sequencing data. We find that PRC-active genes have a greater cell-to-cell variation in expression than active genes with the same mean expression levels, and validate these results by knockout experiments. We also show that PRCactive 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.

Keywords:

Base Sequence, Gene Expression Regulation, Genetic Markers, Genetic Transcription, Knockout Mice, Messenger RNA, Polycomb Repressive Complex 1, Polycomb-Group Proteins, Tumor Cell Line, Ubiquitin-Protein Ligases, Animals, Mice

Source:

Nature Communications

ISSN:

2041-1723

Publisher:

Nature Publishing Group

Volume:

Number:

Page Range:

Date:

26 June 2017

Official Publication: