Genetic and epigenetic mutations affect the DNA binding capability of human ZFP57 in transient neonatal diabetes type 1
Open Access
- 13 March 2013
- journal article
- research article
- Published by Wiley in FEBS Letters
- Vol. 587 (10) , 1474-1481
Abstract
In the mouse, ZFP57 contains three classical Cys2His2 zinc finger domains (ZF) and recognizes the methylated TGCmetCGC 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.Keywords
Funding Information
- Programma MERIT (RBNE08HWLZ_014)
- MIUR PRIN 2009 (GGP11122)
- Telethon-Italia
This publication has 21 references indexed in Scilit:
- An atomic model of Zfp57 recognition of CpG methylation within a specific DNA sequenceGenes & Development, 2012
- Characterization of Novel Paternal ncRNAs at the Plagl1 Locus, Including Hymai, Predicted to Interact with Regulators of Active ChromatinPLOS ONE, 2012
- Zinc Finger Protein ZFP57 Requires Its Co-factor to Recruit DNA Methyltransferases and Maintains DNA Methylation Imprint in Embryonic Stem Cells via Its Transcriptional Repression DomainJournal of Biological Chemistry, 2012
- In Embryonic Stem Cells, ZFP57/KAP1 Recognize a Methylated Hexanucleotide to Affect Chromatin and DNA Methylation of Imprinting Control RegionsMolecular Cell, 2011
- Functional Analysis of KAP1 Genomic RecruitmentMolecular and Cellular Biology, 2011
- A Maternal-Zygotic Effect Gene, Zfp57, Maintains Both Maternal and Paternal ImprintsDevelopmental Cell, 2008
- Hypomethylation of multiple imprinted loci in individuals with transient neonatal diabetes is associated with mutations in ZFP57Nature Genetics, 2008
- A Novel Type of Zinc Finger DNA Binding Domain in the Agrobacterium tumefaciens Transcriptional Regulator RosBiochemistry, 2006
- Identification of Zfp-57 as a downstream molecule of STAT3 and Oct-3/4 in embryonic stem cellsBiochemical and Biophysical Research Communications, 2005
- Identification and Characterization of ZFP-57, a Novel Zinc Finger Transcription Factor in the Mammalian Peripheral Nervous SystemJournal of Biological Chemistry, 2004