title: Transcription Factor hDREF Is a Novel SUMO E3 Ligase of Mi2α.
abstract: 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 Mi2α, 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 Mi2α from chromatin, whereas a SUMOylation-defective Mi2α mutant remained tightly bound to chromatin. Chromatin immunoprecipitation and quantitative RT-PCR analysis demonstrated that Mi2α 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 Mi2α. These data indicate that hDREF might incite transcriptional activation by SUMOylating Mi2α, resulting in the dissociation of Mi2α from the gene loci. We propose a novel mechanism for maintaining constitutively active states of a number of hDREF target genes through SUMOylation.
authors.affiliation: From the Graduate School of Life Science, University of Hyogo, 3-2-1 Koto, Kamigori, Hyogo 678-1297, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamashita
authors.affiliation: From the Graduate School of Life Science, University of Hyogo, 3-2-1 Koto, Kamigori, Hyogo 678-1297, Japan.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Moriuchi
authors.affiliation: From the Graduate School of Life Science, University of Hyogo, 3-2-1 Koto, Kamigori, Hyogo 678-1297, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Osumi
authors.affiliation: From the Graduate School of Life Science, University of Hyogo, 3-2-1 Koto, Kamigori, Hyogo 678-1297, Japan fhirose@sci.u-hyogo.ac.jp.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Hirose
mesh_terms: D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D047369:Chromatin Immunoprecipitation; D004261:DNA Replication; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D001324:Autoantigens; C115323:CHD4 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D025841:Small Ubiquitin-Related Modifier Proteins; D014157:Transcription Factors; C518505:ZBED1 protein, human; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex
keywords: E3 SUMO ligase; Mi2alpha; gene regulation; hDREF; nucleosome remodeling deacetylase (NuRD); sumoylation; transcription factor; transcription regulation