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Monocyte-to-macrophage differentiation is defined by gain and loss of DNA methylation at transcription factor binding sites

ABSTRACT: Macrophages and their precursors monocytes play a key role in inflammation and chronic inflammatory disorders. Monocyte-to-macrophage differentiation and activation programs are accompanied by significant epigenetic remodeling where DNA methylation associates with cell development and identity. Here we show that confined local gain and loss of DNA methylation at transcription factor binding sites as a key characteristic of macrophage identity. Using the Illumina 450k array with a paired epigenome-wide analysis in combination with public whole-genome sequencing data we found that differential DNA methylation was typically highly localized to single CpGs or very short regions that are enriched for lineage specific enhancers. Furthermore, differentially methylated CpGs were located at sites characterized by increased binding of transcription factors known to be involved in monocyte-to-macrophage differentiation including C/EBP and ETS for gain and AP-1 for loss-of-methylation. Our study highlights subtle, highly localized remodeling of DNA methylation at regulatory regions as key in understanding cell differentiation and, potentially, disease mechanisms.

ORGANISM(S): Homo sapiens

PROVIDER: GSE118696 | GEO | 2019/08/17

REPOSITORIES: GEO

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