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| Status |
Public on Aug 17, 2019 |
| Title |
Monocyte-to-macrophage differentiation is defined by gain and loss of DNA methylation at transcription factor binding sites |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by array
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| Summary |
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.
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| Overall design |
Bisulphite converted DNA from the 24 samples (from 4 donors: monocytes, macrophages, M(LPS+IFNγ), M(IL-4), M(oxLDL), M(acLDL)) were hybridised to the Illumina Infinium 450k Human Methylation Beadchip
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| Contributor(s) |
Dekkers KF, Neele AE, Jukema JW, Heijmans BT, de Winther MP |
| Citation missing |
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| Submission date |
Aug 17, 2018 |
| Last update date |
Aug 18, 2019 |
| Contact name |
Koen Dekkers |
| Organization name |
Leiden University Medical Center
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| Street address |
Room S5-08, P.O. Box 9600
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| City |
Leiden |
| ZIP/Postal code |
2300 RC |
| Country |
Netherlands |
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| Platforms (1) |
| GPL13534 |
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA486502 |
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