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- Title
Flipping between Polycomb repressed and active transcriptional states introduces noise in gene expression.
- Authors
Kar, Gozde; Jong Kyoung Kim; Kolodziejczyk, Aleksandra A.; Natarajan, Kedar Nath; Triglia, Elena Torlai; Mifsud, Borbala; Elderkin, Sarah; Marioni, John C.; Pombo, Ana; Teichmann, Sarah 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 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.
- Publication
Nature Communications, 2017, Vol 8, Issue 6, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-017-00052-2