Recognition of Oxidized 5‐Methylcytosine Derivatives in DNA by Natural and Engineered Protein Scaffolds

Methylation of genomic cytosine to 5‐methylcytosine is a central regulatory element of mammalian gene expression with important roles in development and disease. 5‐methylcytosine can be actively reversed to cytosine via oxidation to 5‐hydroxymethyl‐, 5‐formyl‐, and 5‐carboxylcytosine by ten‐eleven‐t...

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Bibliographic Details
Published in:Chemical record 2018-01, Vol.18 (1), p.105-116
Main Authors: Muñoz‐López, Álvaro, Summerer, Daniel
Format: Article
Language:English
Subjects:
Base excision repair
Bases (nucleic acids)
Chromatin
Cytosine
Deoxyribonucleic acid
Derivatives
Dilution
DNA
DNA methylation
DNA-binding protein
Epigenetics
Gene expression
Molecular Recognition
Oxidation
Protein-DNA Interactions
Proteins
Recognition
Scaffolds
Structure-function relationships
TET dioxygenase
Transcription
Translocation
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Summary:Methylation of genomic cytosine to 5‐methylcytosine is a central regulatory element of mammalian gene expression with important roles in development and disease. 5‐methylcytosine can be actively reversed to cytosine via oxidation to 5‐hydroxymethyl‐, 5‐formyl‐, and 5‐carboxylcytosine by ten‐eleven‐translocation dioxygenases and subsequent base excision repair or replication‐dependent dilution. Moreover, the oxidized 5‐methylcytosine derivatives are potential epigenetic marks with unique biological roles. Key to a better understanding of these roles are insights into the interactions of the nucleobases with DNA‐binding protein scaffolds: Natural scaffolds involved in transcription, 5‐methylcytosine‐reading and ‐editing as well as general chromatin organization can be selectively recruited or repulsed by oxidized 5‐methylcytosines, forming the basis of their biological functions. Moreover, designer protein scaffolds engineered for the selective recognition of oxidized 5‐methylcytosines are valuable tools to analyze their genomic levels and distribution. Here, we review recent structural and functional insights into the molecular recognition of oxidized 5‐methylcytosine derivatives in DNA by selected protein scaffolds. TET‐mediated oxidation of 5‐methylcytosine enriches the epigenetic information encoded by mammalian DNA. This information controls chromatin organization and transcription by specific protein‐DNA interactions. Here, we review studies that elucidate how proteins interact with oxidized 5‐methylcytosine derivatives, and how new protein scaffolds can be engineered for their detection in DNA.
ISSN:1527-8999
1528-0691
DOI:10.1002/tcr.201700088