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DOI10.1038/s41467-019-08435-3
Flipping between Polycomb repressed and active transcriptional states introduces noise in gene expression
Kar, Gozde1; Kim, Jong Kyoung1,2; Kolodziejczyk, Aleksandra A.1,3; Natarajan, Kedar Nath1,3; Triglia, Elena Torlai4; Mifsud, Borbala5,6,7; Elderkin, Sarah8; Marioni, John C.1,3,9; Pombo, Ana4; Teichmann, Sarah A.1,3
2019-02-14
发表期刊NATURE COMMUNICATIONS
ISSN2041-1723
出版年2017
卷号8
文章类型Article
语种英语
国家England; South Korea; Germany
英文摘要

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.


领域资源环境
收录类别SCI-E
WOS记录号WOS:000404026900006
WOS关键词EMBRYONIC STEM-CELLS ; RNA-POLYMERASE-II ; MOUSE ES CELLS ; SINGLE-CELL ; REGULATORY CIRCUITRY ; SEQUENCING DATA ; GENOME-WIDE ; BURST SIZE ; PLURIPOTENT ; CHROMATIN
WOS类目Multidisciplinary Sciences
WOS研究方向Science & Technology - Other Topics
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文献类型期刊论文
条目标识符http://119.78.100.173/C666/handle/2XK7JSWQ/204223
专题资源环境科学
作者单位1.EBI, EMBL, Wellcome Trust Genome Campus, Cambridge CB10 1SD, England;
2.DGIST, Dept New Biol, Daegu 42988, South Korea;
3.Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SA, England;
4.Max Delbruck Ctr Mol Med, Berlin Inst Med Syst Biol, Epigenet Regulat & Chromatin Architecture Grp, Robert Roessle Str, D-13125 Berlin, Germany;
5.Canc Res UK London Res Inst, 44 Lincolns Inn Fields, London WC2A 3LY, England;
6.UCL, Dept Genet Evolut & Environm, Gower St, London WC1E 6BT, England;
7.Queen Mary Univ London, William Harvey Res Inst, Charterhouse Sq, London EC1M 6BQ, England;
8.Babraham Inst, Nucl Dynam Programme, Babraham Res Campus, Cambridge CB22 3AT, England;
9.Univ Cambridge, Li Ka Shing Ctr, Canc Res UK Cambridge Inst, Robinson Way, Cambridge CB2 0RE, England
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GB/T 7714
Kar, Gozde,Kim, Jong Kyoung,Kolodziejczyk, Aleksandra A.,et al. Flipping between Polycomb repressed and active transcriptional states introduces noise in gene expression[J]. NATURE COMMUNICATIONS,2019,8.
APA Kar, Gozde.,Kim, Jong Kyoung.,Kolodziejczyk, Aleksandra A..,Natarajan, Kedar Nath.,Triglia, Elena Torlai.,...&Teichmann, Sarah A..(2019).Flipping between Polycomb repressed and active transcriptional states introduces noise in gene expression.NATURE COMMUNICATIONS,8.
MLA Kar, Gozde,et al."Flipping between Polycomb repressed and active transcriptional states introduces noise in gene expression".NATURE COMMUNICATIONS 8(2019).
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