Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types

Ecker, Simone; Merkel, Angelika; BLUEPRINT Consortium; Paul, Dirk S.

doi:http://dx.doi.org/10.1186/s13059-017-1156-8

Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types

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Citació

Ecker S, Chen L, Pancaldi V, Bagger FO, Fernández JM, Carrillo de Santa Pau E et al. Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types. Genome Biology. 2017;18:18. DOI: 10.1186/s13059-017-1156-8

Resum

Background: A healthy immune system requires immune cells that adapt rapidly to environmental challenges. This phenotypic plasticity can be mediated by transcriptional and epigenetic variability. Results: We apply a novel analytical approach to measure and compare transcriptional and epigenetic variability genome-wide across CD14+CD16− monocytes, CD66b+CD16+ neutrophils, and CD4+CD45RA+ naïve T cells from the same 125 healthy individuals. We discover substantially increased variability in neutrophils compared to monocytes and T cells. In neutrophils, genes with hypervariable expression are found to be implicated in key immune pathways and are associated with cellular properties and environmental exposure. We also observe increased sex-specific gene expression differences in neutrophils. Neutrophil-specific DNA methylation hypervariable sites are enriched at dynamic chromatin regions and active enhancers. Conclusions: Our data highlight the importance of transcriptional and epigenetic variability for the key role of neutrophils as the first responders to inflammatory stimuli. We provide a resource to enable further functional studies into the plasticity of immune cells, which can be accessed from: http://blueprint-dev.bioinfo.cnio.es/WP10/hypervariability.