Immunity
Volume 54, Issue 11, 9 November 2021, Pages 2465-2480.e5
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Article
DNA methylation signatures reveal that distinct combinations of transcription factors specify human immune cell epigenetic identity

https://doi.org/10.1016/j.immuni.2021.10.001Get rights and content
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Highlights

  • Identifies differential DNA methylation signatures of six human immune cell types

  • Combinations of transcription factor motifs associate with lineage-specific methylation

  • EBF1 binding coincides with DNA hypomethylated sites in human B cells

  • Adaptive and innate immune cells show distinct methylation and gene expression patterns

Summary

Epigenetic reprogramming underlies specification of immune cell lineages, but patterns that uniquely define immune cell types and the mechanisms by which they are established remain unclear. Here, we identified lineage-specific DNA methylation signatures of six immune cell types from human peripheral blood and determined their relationship to other epigenetic and transcriptomic patterns. Sites of lineage-specific hypomethylation were associated with distinct combinations of transcription factors in each cell type. By contrast, sites of lineage-specific hypermethylation were restricted mostly to adaptive immune cells. PU.1 binding sites were associated with lineage-specific hypo- and hypermethylation in different cell types, suggesting that it regulates DNA methylation in a context-dependent manner. These observations indicate that innate and adaptive immune lineages are specified by distinct epigenetic mechanisms via combinatorial and context-dependent use of key transcription factors. The cell-specific epigenomics and transcriptional patterns identified serve as a foundation for future studies on immune dysregulation in diseases and aging.

Keywords

DNA methylation
epigenetics
human immunity
lymphocytes
innate cells
transcription factors
gene expression

Data and code availability

  • Raw and normalized DNA methylation and RNASeq data and EBF1 ChIP-Seq data have been deposited in GEO and are publicly available as of the date of publication. Accession numbers are listed in the key resources table

  • This paper does not report original code.

  • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request

Cited by (0)

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Present address: Institute of Medical Bioinformatics and Systems Medicine, Division of Pediatric Hematology and Oncology, Medical Center, University of Freiburg, Freiburg, Germany

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Lead contact