Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università degli Studi di Napoli, Via Vivaldi 43, 81100 Caserta, Italy.
FEBS Lett. 2013 May 21;587(10):1474-81. doi: 10.1016/j.febslet.2013.02.045. Epub 2013 Mar 13.
In the mouse, ZFP57 contains three classical Cys2His2 zinc finger domains (ZF) and recognizes the methylated TGC(met)CGC target sequence using the first and the second ZFs. In this study, we demonstrate that the human ZFP57 (hZFP57) containing six Cys2His2 ZFs, binds the same methylated sequence through the third and the fourth ZFs, and identify the aminoacids critical for DNA interaction. In addition, we present evidences indicating that hZFP57 mutations and hypomethylation of the TNDM1 ICR both associated with Transient Neonatal Diabetes Mellitus type 1 result in loss of hZFP57 binding to the TNDM1 locus, likely causing PLAGL1 activation.
在小鼠中，ZFP57 包含三个经典的 Cys2His2 锌指结构域（ZF），并使用第一个和第二个 ZF 识别甲基化的 TGC（met）CGC 靶序列。在这项研究中，我们证明了含有六个 Cys2His2 ZF 的人 ZFP57（hZFP57）通过第三个和第四个 ZF 结合相同的甲基化序列，并确定了与 DNA 相互作用有关的关键氨基酸。此外，我们还提供了证据表明，与 1 型短暂性新生儿糖尿病相关的 TNDM1 ICR 突变和低甲基化导致 hZFP57 与 TNDM1 基因座结合的丢失，可能导致 PLAGL1 的激活。
