title: Genetic and epigenetic mutations affect the DNA binding capability of human ZFP57 in transient neonatal diabetes type 1.
abstract: 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.
authors.affiliation: Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università degli Studi di Napoli, Via Vivaldi 43, 81100 Caserta, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Baglivo
authors.forename: Sabrina
authors.initials: S
authors.lastname: Esposito
authors.forename: Lucia
authors.initials: L
authors.lastname: De Cesare
authors.forename: Angela
authors.initials: A
authors.lastname: Sparago
authors.forename: Zahra
authors.initials: Z
authors.lastname: Anvar
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Riso
authors.forename: Marco
authors.initials: M
authors.lastname: Cammisa
authors.forename: Roberto
authors.initials: R
authors.lastname: Fattorusso
authors.forename: Giovanna
authors.initials: G
authors.lastname: Grimaldi
authors.forename: Andrea
authors.initials: A
authors.lastname: Riccio
authors.forename: Paolo V
authors.initials: PV
authors.lastname: Pedone
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism*; D019175:DNA Methylation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000235:genetics* / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology*; D011485:Protein Binding / Q000235:genetics; D012097:Repressor Proteins; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C106464:PLAGL1 protein, human; D012097:Repressor Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C531063:ZFP57 protein, human; D004247:DNA