Abstract
Background
Population phenotypic variation can arise from genetic differences between individuals, or from cellular heterogeneity in an isogenic group of cells or organisms. The emergence of gene expression differences between genetically identical cells is referred to as gene expression noise, the sources of which are not well understood.
Results
In this work, by studying gene expression noise between multiple cell lineages and mammalian species, we find consistent evidence of a role for CpG islands as sources of gene expression noise. Variation in noise among CpG island promoters can be partially attributed to differences in island size, in which short islands have noisier gene expression. Building on these findings, we investigate the potential for short CpG islands to act as fast response elements to environmental stimuli. Specifically, we find that these islands are enriched amongst primary response genes in SWI/SNF-independent stimuli, suggesting that expression noise is an indicator of promoter responsiveness.
Conclusions
Thus, through the integration of single-cell RNA expression profiling, chromatin landscape and temporal gene expression dynamics, we have uncovered a role for short CpG island promoters as fast response elements.
Population phenotypic variation can arise from genetic differences between individuals, or from cellular heterogeneity in an isogenic group of cells or organisms. The emergence of gene expression differences between genetically identical cells is referred to as gene expression noise, the sources of which are not well understood.
Results
In this work, by studying gene expression noise between multiple cell lineages and mammalian species, we find consistent evidence of a role for CpG islands as sources of gene expression noise. Variation in noise among CpG island promoters can be partially attributed to differences in island size, in which short islands have noisier gene expression. Building on these findings, we investigate the potential for short CpG islands to act as fast response elements to environmental stimuli. Specifically, we find that these islands are enriched amongst primary response genes in SWI/SNF-independent stimuli, suggesting that expression noise is an indicator of promoter responsiveness.
Conclusions
Thus, through the integration of single-cell RNA expression profiling, chromatin landscape and temporal gene expression dynamics, we have uncovered a role for short CpG island promoters as fast response elements.
| Original language | English |
|---|---|
| Article number | 18 |
| Number of pages | 13 |
| Journal | Genome Biology |
| Volume | 19 |
| Early online date | 26 Jun 2018 |
| DOIs | |
| Publication status | Published - Jun 2018 |
Bibliographical note
We wish to thank Wolf Reik, Ferdinand von Meyenn and Aaron T. Lun for kindly donating single-cell gene expression data from human ESCs. The authors also wish to thank Sarah Thorpe and Christina Ernst for critical reading of the manuscript.Funding
MDM was supported by the Wellcome Trust (grant 105045/Z/14/Z). JCM was supported by core funding from the European Molecular Biology Laboratory and from Cancer Research UK (award number 17197).
Data Availability Statement
All data sets can be obtained via the appropriate accession number for each study or website where relevant:
Mus musculus naive Cd4+ T cells: Stubbington MJT, et al. T cell fate and clonality inference from single-cell transcriptomes. Array Express. E-MTAB-3857.
Mus musculus embryonic stem cells: Grun D, et al. Validation of noise models for single-cell transcriptomics. GEO. GSE54695.
Mus musculus embryonic stem cells: Kolodziejczyk AA, et al. Single-cell RNA-sequencing of pluripotent states unlocks modular transcriptional variation. Array Express. E-MTAB-2600.
Homo sapiens embryonic stem cells: von Meyenn F, Lun AT, Marioni JC, Reik W. Array Express. E-MTAB-6819.
Homo sapiens pancreatic islet cells: Lawlor N, et al. Single-cell transcriptomes identify human islet cell signatures and reveal cell-type–specific expression changes in type 2 diabetes. GEO. GSE86473.
Mus musculus bone marrow-derived dendritic cells: Shalek AK, et al. Single-cell RNA-seq reveals dynamic paracrine control of cellular variation. GEO. GSE48968.
Homo sapiens MCF-7 breast adenocarcinoma cells: Baran-Gale J, et al. An integrative transcriptomics approach identifies miR-503 as a candidate master regulator of the oestrogen response in MCF-7 breast cancer cells. GEO. GSE78169.
Homo sapiens monocyte-derived dendritic cells: Diehl WE, et al. Ebola virus glycoprotein with increased infectivity dominated the 2013–2016 epidemic. GEO. GSE84865.
Homo sapiens CAGE-seq data sets: Forrest ARR, et al. FANTOM5. http://fantom.gsc.riken.jp/5/datafiles/latest/extra/CAGE_peaks
Keywords
- Gene expression noise
- Single cell
- Promoter response
Access to Document
- Morgan_etal_GB_CpG_island_composition_VOR
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