Transcription Factor hDREF Is a Novel SUMO E3 Ligase of Mi2?.
The human transcription factor DNA replication-related element-binding factor (hDREF) is essential for the transcription of a number of housekeeping genes. The mechanisms underlying constitutively active transcription by hDREF were unclear. Here, we provide evidence that hDREF possesses small ubiquitin-like modifier (SUMO) ligase activity and can specifically SUMOylate Mi2?, an ATP-dependent ... DNA helicase in the nucleosome remodeling and deacetylation complex. Moreover, immunofluorescent staining and biochemical analyses showed that coexpression of hDREF and SUMO-1 resulted in dissociation of Mi2? from chromatin, whereas a SUMOylation-defective Mi2? mutant remained tightly bound to chromatin. Chromatin immunoprecipitation and quantitative RT-PCR analysis demonstrated that Mi2? expression diminished transcription of the ribosomal protein genes, which are positively regulated by hDREF. In contrast, coexpression of hDREF and SUMO-1 suppressed the transcriptional repression by Mi2?. These data indicate that hDREF might incite transcriptional activation by SUMOylating Mi2?, resulting in the dissociation of Mi2? from the gene loci. We propose a novel mechanism for maintaining constitutively active states of a number of hDREF target genes through SUMOylation.
Mesh Terms:
Autoantigens, Blotting, Western, Chromatin Immunoprecipitation, DNA Replication, Fluorescent Antibody Technique, Gene Expression Regulation, HeLa Cells, Humans, Immunoenzyme Techniques, Immunoprecipitation, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Promoter Regions, Genetic, Protein Binding, Protein Processing, Post-Translational, RNA, Messenger, RNA, Small Interfering, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Small Ubiquitin-Related Modifier Proteins, Sumoylation, Transcription Factors, Transcriptional Activation
Autoantigens, Blotting, Western, Chromatin Immunoprecipitation, DNA Replication, Fluorescent Antibody Technique, Gene Expression Regulation, HeLa Cells, Humans, Immunoenzyme Techniques, Immunoprecipitation, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Promoter Regions, Genetic, Protein Binding, Protein Processing, Post-Translational, RNA, Messenger, RNA, Small Interfering, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Small Ubiquitin-Related Modifier Proteins, Sumoylation, Transcription Factors, Transcriptional Activation
J Biol Chem
Date: May. 27, 2016
PubMed ID: 27068747
View in: Pubmed Google Scholar
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