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SHARE-seq reveals chromatin potential

Nature Reviews Genetics volume 22, page 2 (2021)Cite this article

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Changes in chromatin accessibility and gene expression underpinning cell fate decisions can be studied using approaches that measure both parameters in the same cell, but such methods are few and have restricted throughput or resolution. Simultaneous high-throughput ATAC and RNA expression with sequencing (SHARE-seq), a new multi-omics method described in Cell, is reported to overcome these limitations.

When applied to adult mouse skin, SHARE-seq generated 34,774 high-quality single-cell paired profiles, and cluster analysis of either chromatin accessibility or gene expression data defined broadly similar cell types. Co-variation patterns between paired profiles were used to infer chromatin peak–target gene associations, and regions with a high density of peak–gene associations were termed domains of regulatory chromatin (DORCs); these regions are enriched for lineage-specifying genes and overlap known super-enhancers. Analysis of hair follicle differentiation revealed that chromatin accessibility at DORCs precedes target gene expression. Indeed, chromatin profiles at DORCs could be used to calculate the most likely future state of target gene expression (that is, the ‘chromatin potential’) of a cell, thereby inferring its potential lineage choices.

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References

Original article

  • Ma, S. et al. Chromatin potential identified by shared single-cell profiling of RNA and chromatin. Cell 183, 1103–1116 (2020)

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  1. Nature Reviews Genetics http://www.nature.com/nrg/

    Dorothy Clyde

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  1. Dorothy Clyde
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Correspondence to Dorothy Clyde.

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Clyde, D. SHARE-seq reveals chromatin potential. Nat Rev Genet 22, 2 (2021). https://doi.org/10.1038/s41576-020-00308-6

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  • DOI: https://doi.org/10.1038/s41576-020-00308-6

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