Genetic and epigenetic mutations affect the DNA binding capability of human ZFP57 in transient neonatal diabetes type 1

► hZFP57 zinc finger 3 and 4 are sufficient for high affinity DNA binding. ► hZFP57 TNDM1 mutations (R248H and H277N) affect DNA binding. ► DNA sequences in the TNDM1 ICR show DNA methylation-dependent binding to hZFP57. ► mZfp57 inactivation results in loss of DNA promoter methylation and Plagl1 activation.