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.
Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism
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Cells, Cultured
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DNA / metabolism*
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DNA Methylation / genetics
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism*
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Diabetes Mellitus / genetics*
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Diabetes Mellitus / metabolism
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Embryonic Stem Cells / metabolism
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Epigenesis, Genetic / genetics
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Epigenesis, Genetic / physiology*
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Humans
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Infant, Newborn
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Infant, Newborn, Diseases / genetics*
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Infant, Newborn, Diseases / metabolism
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Mice
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Molecular Sequence Data
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Mutation / physiology*
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Protein Binding / genetics
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Repressor Proteins
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Sequence Homology, Amino Acid
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Transcription Factors / genetics*
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Transcription Factors / metabolism*
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism
Substances
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Cell Cycle Proteins
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DNA-Binding Proteins
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PLAGL1 protein, human
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Repressor Proteins
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Transcription Factors
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Tumor Suppressor Proteins
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ZFP57 protein, human
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DNA
Supplementary concepts
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Diabetes Mellitus, Transient Neonatal, 1