Journal of Molecular Biology
Volume 432, Issue 6, 13 March 2020, Pages 1792-1800
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Review
Identifying Readers for (hydroxy)methylated DNA Using Quantitative Interaction Proteomics: Advances and Challenges Ahead

https://doi.org/10.1016/j.jmb.2019.12.014Get rights and content
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Highlights

  • DNA methylation is an important epigenetic modification that regulates gene expression.

  • Quantitative proteomics has enabled the identification of “readers” for (hydroxy)methylated DNA.

  • Integrative omics will unveil mechanisms of DNA methylation-mediated gene regulation.

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.

Keywords

DNA methylation
Quantitative interaction proteomics
Single-locus proteomics
(hydroxy)methylation readers

Abbreviations

DNMT
DNA methyltransferases
TET
Ten eleven translocation enzymes
MS
Mass spectrometry
mESC
Mouse embryonic stem cells
ChIP
Chromatin immunoprecipitation
MBD
Methyl-binding proteins
PICh
proteomics of isolated chromatin segments
LNA
Locked nucleic acid

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