Genetic and epigenetic mutations affect the DNA binding capability of human ZFP57 in transient neonatal diabetes type 1.
Ilaria Baglivo, Sabrina Esposito, Lucia De Cesare, Angela Sparago, Zahra Anvar, Vincenzo Riso, Marco Cammisa, Roberto Fattorusso, Giovanna Grimaldi, Andrea Riccio, Paolo V Pedone
Author Information
Ilaria Baglivo: Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università degli Studi di Napoli, Via Vivaldi 43, 81100 Caserta, Italy.
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 humanZFP57 (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.
References
Biochemistry. 2006 Aug 29;45(34):10394-405
[PMID: 16922516]
Mol Cell. 2011 Nov 4;44(3):361-72
[PMID: 22055183]
