Global modulation in DNA epigenetics during pro-inflammatory macrophage activation

Nikhil Jain*, Tamar Shahal, Tslil Gabrieli, Noa Gilat, Dmitry Torchinsky, Yael Michaeli, Viola Vogel, Yuval Ebenstein

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

DNA methylation patterns create distinct gene-expression profiles. These patterns are maintained after cell division, thus enabling the differentiation and maintenance of multiple cell types from the same genome sequence. The advantage of this mechanism for transcriptional control is that chemical-encoding allows to rapidly establish new epigenetic patterns ‘on-demand’ through enzymatic methylation and demethylation of DNA. Here we show that this feature is associated with the fast response of macrophages during their pro-inflammatory activation. By using a combination of mass spectroscopy and single-molecule imaging to quantify global epigenetic changes in the genomes of primary macrophages, we followed three distinct DNA marks (methylated, hydroxymethylated and unmethylated), involved in establishing new DNA methylation patterns during pro-inflammatory activation. The observed epigenetic modulation together with gene-expression data generated for the involved enzymatic machinery may suggest that de-methylation upon LPS-activation starts with oxidation of methylated CpGs, followed by excision-repair of these oxidized bases and their replacement with unmodified cytosine.

Original languageEnglish
Pages (from-to)1183-1193
Number of pages11
JournalEpigenetics
Volume14
Issue number12
DOIs
StatePublished - 2 Dec 2019

Funding

FundersFunder number
BeyondSeq consortium
SNF NCCR ‘Molecular Systems Engineering
European Molecular Biology Organization
Horizon 2020 Framework Programme337830
European Commission634890
European Research Council
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungIZK0Z3_174260, CR32I3_156931
Israel Science Foundation1902/12

    Keywords

    • DNA methylation
    • Macrophage activation
    • RNA sequencing
    • mass spectroscopy
    • single-molecule imaging

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