Title: Reversible DNA-Protein Cross-Linking at Epigenetic DNA Marks.

Authors: Ji, Shaofei; Shao, Hongzhao; Han, Qiyuan; Seiler, Christopher L; Tretyakova, Natalia Y

Published In Angew Chem Int Ed Engl, (2017 Nov 06)

Abstract: 5-Formylcytosine (5fC) is an endogenous DNA modification frequently found within regulatory elements of mammalian genes. Although 5fC is an oxidation product of 5-methylcytosine (5mC), the two epigenetic marks show distinct genome-wide distributions and protein affinities, suggesting that they perform different functions in epigenetic signaling. A unique feature of 5fC is the presence of a potentially reactive aldehyde group in its structure. Herein, we show that 5fC bases in DNA readily form Schiff-base conjugates with Lys side chains of nuclear proteins in vitro and in vivo. These covalent protein-DNA complexes are reversible (t1/2 =1.8 h), suggesting that they contribute to transcriptional regulation and chromatin remodeling. On the other hand, 5fC-mediated DNA-protein cross-links, if present at replication forks or actively transcribed regions, may interfere with DNA replication and transcription.

PubMed ID: 28898504

MeSH Terms: 5-Methylcytosine/chemistry; Cytosine/analogs & derivatives; Cytosine/chemistry; DNA/chemistry*; Electrophoresis, Polyacrylamide Gel; Epigenesis, Genetic*; Gene Expression Regulation; Hydrogen-Ion Concentration; Proteins/chemistry*; Spectrometry, Mass, Electrospray Ionization; Temperature; Transcription, Genetic