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- Title
Reversible DNA-Protein Cross-Linking at Epigenetic DNA Marks.
- Authors
Ji, Shaofei; Shao, Hongzhao; Han, Qiyuan; Seiler, Christopher L.; Tretyakova, Natalia Y.
- 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.
- Subjects
DNA-protein interactions; PROTEIN crosslinking; EPIGENETICS; DNA modification &; restriction; CYTOSINE
- Publication
Angewandte Chemie, 2017, Vol 129, Issue 45, p14318
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.201708286