Abstract
In mammalian cells, DNA methylation is associated with heritable and stable gene repression, mediated in part by methyl-CpG-binding domain (MBD) proteins that recruit corepressors to modify chromatin. MBD1 protein, a member of the MBD family, forms a complex with SETDB1 histone methylase to silence transcription at target promoters by methylation of lysine 9 of histone H3. How MBD1-mediated transcriptional repression is regulated is currently unknown. Here we show that MBD1 is a target for sumoylation by PIAS1 (Protein Inhibitors of Activated STAT 1) and PIAS3 E3 SUMO (small ubiquitin-like modifier)-ligases, at two conserved lysine residues within the C-terminus of MBD1. Although sumoylated MBD1 binds to methylated DNA, it does not incorporate into a complex with SETDB1 and does not efficiently repress transcription of a target gene, p53BP2, in HeLa cells. Our data suggest that transcriptional silencing by MBD1 is regulated by a PIAS-mediated conjugation of SUMO1, which antagonizes the formation of a repressive complex with SETDB1.
Publication types
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Research Support, Non-U.S. Gov't
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Retracted Publication
MeSH terms
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Amino Acid Sequence
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Apoptosis Regulatory Proteins
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Carrier Proteins / physiology
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Chromatin / genetics
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Chromatin / physiology
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Conserved Sequence
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DNA Methylation
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DNA-Binding Proteins / metabolism
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DNA-Binding Proteins / physiology*
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Down-Regulation
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Gene Silencing
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HeLa Cells
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Histone-Lysine N-Methyltransferase
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Histones / metabolism
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Humans
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Molecular Chaperones / genetics
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Molecular Chaperones / physiology*
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Molecular Sequence Data
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Protein Binding
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Protein Inhibitors of Activated STAT / genetics
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Protein Inhibitors of Activated STAT / physiology*
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Protein Methyltransferases / metabolism
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SUMO-1 Protein
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Sequence Homology, Amino Acid
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Small Ubiquitin-Related Modifier Proteins / genetics
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Small Ubiquitin-Related Modifier Proteins / physiology*
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Transcription Factors / metabolism
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Transcription Factors / physiology*
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Transcription, Genetic*
Substances
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Apoptosis Regulatory Proteins
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Carrier Proteins
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Chromatin
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DNA-Binding Proteins
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Histones
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MBD1 protein, human
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Molecular Chaperones
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PIAS1 protein, human
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PIAS3 protein, human
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Protein Inhibitors of Activated STAT
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SUMO-1 Protein
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SUMO1 protein, human
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Small Ubiquitin-Related Modifier Proteins
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TP53BP2 protein, human
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Transcription Factors
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Protein Methyltransferases
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Histone-Lysine N-Methyltransferase
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SETDB1 protein, human