DNA methylation signatures reveal that distinct combinations of transcription factors specify human immune cell epigenetic identity.

Autor:	Roy R; Laboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, MD, USA., Ramamoorthy S; Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany., Shapiro BD; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA; Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA., Kaileh M; Laboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, MD, USA., Hernandez D; Laboratory of Neurogenetics, National Institute on Aging, Baltimore, MD, USA., Sarantopoulou D; Laboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, MD, USA., Arepalli S; Laboratory of Neurogenetics, National Institute on Aging, Baltimore, MD, USA., Boller S; Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany., Singh A; Laboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, MD, USA., Bektas A; Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA., Kim J; Laboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, MD, USA., Moore AZ; Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA., Tanaka T; Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA., McKelvey J; Clinical Research Core, National Institute on Aging, Baltimore, MD, USA., Zukley L; Clinical Research Core, National Institute on Aging, Baltimore, MD, USA., Nguyen C; Flow Cytometry Unit, National Institute on Aging, Baltimore, MD, USA., Wallace T; Flow Cytometry Unit, National Institute on Aging, Baltimore, MD, USA., Dunn C; Flow Cytometry Unit, National Institute on Aging, Baltimore, MD, USA., Wersto R; Flow Cytometry Unit, National Institute on Aging, Baltimore, MD, USA., Wood W; Laboratory of Genetics & Genomics, National Institute on Aging, Baltimore, MD, USA., Piao Y; Laboratory of Genetics & Genomics, National Institute on Aging, Baltimore, MD, USA., Becker KG; Laboratory of Genetics & Genomics, National Institute on Aging, Baltimore, MD, USA., Coletta C; Laboratory of Genetics & Genomics, National Institute on Aging, Baltimore, MD, USA., De S; Laboratory of Genetics & Genomics, National Institute on Aging, Baltimore, MD, USA., Sen JM; Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD, USA., Battle A; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA; Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA., Weng NP; Laboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, MD, USA., Grosschedl R; Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany., Ferrucci L; Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA., Sen R; Laboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, MD, USA. Electronic address: senranja@grc.nia.nih.gov.
Jazyk:	angličtina
Zdroj:	Immunity [Immunity] 2021 Nov 09; Vol. 54 (11), pp. 2465-2480.e5. Date of Electronic Publication: 2021 Oct 26.
DOI:	10.1016/j.immuni.2021.10.001
Abstrakt:	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. Competing Interests: Declaration of interests A. Battle holds stock in Google and is a consultant for Third Rock Ventures. (Published by Elsevier Inc.)
Databáze:	MEDLINE
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