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PDBsum entry 4r2q
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DNA binding protein/DNA
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PDB id
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4r2q
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References listed in PDB file
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Key reference
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Title
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Wilms tumor protein recognizes 5-Carboxylcytosine within a specific DNA sequence.
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Authors
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H.Hashimoto,
Y.O.Olanrewaju,
Y.Zheng,
G.G.Wilson,
X.Zhang,
X.Cheng.
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Ref.
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Genes Dev, 2014,
28,
2304-2313.
[DOI no: ]
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PubMed id
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Abstract
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In mammalian DNA, cytosine occurs in several chemical forms, including
unmodified cytosine (C), 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC),
5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). 5mC is a major epigenetic
signal that acts to regulate gene expression. 5hmC, 5fC, and 5caC are oxidized
derivatives that might also act as distinct epigenetic signals. We investigated
the response of the zinc finger DNA-binding domains of transcription factors
early growth response protein 1 (Egr1) and Wilms tumor protein 1 (WT1) to
different forms of modified cytosine within their recognition sequence,
5'-GCG(T/G)GGGCG-3'. Both displayed high affinity for the sequence when C or 5mC
was present and much reduced affinity when 5hmC or 5fC was present, indicating
that they differentiate primarily oxidized C from unoxidized C, rather than
methylated C from unmethylated C. 5caC affected the two proteins differently,
abolishing binding by Egr1 but not by WT1. We ascribe this difference to
electrostatic interactions in the binding sites. In Egr1, a negatively charged
glutamate conflicts with the negatively charged carboxylate of 5caC, whereas the
corresponding glutamine of WT1 interacts with this group favorably. Our analyses
shows that zinc finger proteins (and their splice variants) can respond in
modulated ways to alternative modifications within their binding sequence.
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