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Flipping between Polycomb repressed and active transcriptional states introduces noise in gene expression
- Flipping between Polycomb repressed and active transcriptional states introduces noise in gene expression
- Kar, Gozde; Kim, Jong Kyoung; Kolodziejczyk, Aleksandra A.; Natarajan, Kedar Nath; Triglia, Elena Torlai; Mifsud, Borbala; Elderkin, Sarah; Marioni, John C.; Pombo, Ana; Teichmann, Sarah A.
- DGIST Authors
- Kim, Jong Kyoung
- Issue Date
- Nature Communications, 8
- Article Type
- Allele; Animal Cell
- 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. © 2017 The Author(s).
- Nature Publishing Group
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