Department of Chemistry, University of Minnesota, Minneapolis, MN, 55455, USA.
Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN, 55455, USA.
Angew Chem Int Ed Engl. 2017 Nov 6;56(45):14130-14134. doi: 10.1002/anie.201708286. Epub 2017 Oct 6.
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 (t =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.
5- 甲酰胞嘧啶（5fC）是一种内源性 DNA 修饰，经常在哺乳动物基因的调控元件中发现。虽然 5fC 是 5- 甲基胞嘧啶（5mC）的氧化产物，但这两种表观遗传标记在全基因组范围内的分布和蛋白质亲和力上表现出明显的差异，表明它们在表观遗传信号转导中发挥不同的功能。5fC 的一个独特特征是其结构中存在潜在的反应性醛基。在此，我们证明 DNA 中的 5fC 碱基在体外和体内与核蛋白的赖氨酸侧链容易形成希夫碱缀合物。这些共价的蛋白质-DNA 复合物是可逆的（t =1.8 h），表明它们有助于转录调控和染色质重塑。另一方面，如果 5fC 介导的 DNA- 蛋白质交联存在于复制叉或活跃转录区域，可能会干扰 DNA 复制和转录。
