Abstract
DNA methylation is an epigenetic modification, which regulates gene expression during cellular differentiation. This important function is thought to be carried out by transcriptional regulators, which are “readers” and effectors of this mark. In recent years, quantitative mass spectrometry-based interaction proteomics technology has emerged as a powerful tool to identify readers for methylated and unmethylated DNA in different cellular contexts. Furthermore, recent technology enables proteome-wide quantification of absolute affinities between proteins and methylated and unmethylated DNA in the context of crude nuclear extracts. Finally, recently developed locus-specific interaction proteomics approaches and modifications thereof facilitate an unbiased proteome characterization of methylated and unmethylated genomic loci in vivo. We summarize these recent findings in this review, and we argue that the integration of all these technologies, with also genomic sequencing-based approaches, will eventually result in a more detailed understanding of the link between DNA methylation and the regulation of transcription in health and disease.
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