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.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882432 | PMC |
http://dx.doi.org/10.1074/jbc.M115.713370 | DOI Listing |
J Biol Chem
May 2016
From the Graduate School of Life Science, University of Hyogo, 3-2-1 Koto, Kamigori, Hyogo 678-1297, Japan
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.
View Article and Find Full Text PDFMol Cell Biol
March 2007
Graduate School of Life Science, University of Hyogo, Kamigori, Hyogo 678-1297, Japan.
Although ribosomal proteins (RPs) are essential cellular constituents in all living organisms, mechanisms underlying regulation of their gene expression in mammals remain unclear. We have established that 22 out of 79 human RP genes contain sequences similar to the human DREF (DNA replication-related element-binding factor; hDREF) binding sequence (hDRE) within 200-bp regions upstream of their transcriptional start sites. Electrophoretic gel mobility shift assays and chromatin immunoprecipitation analysis indicated that hDREF binds to hDRE-like sequences in the RP genes both in vitro and in vivo.
View Article and Find Full Text PDFJ Biol Chem
March 2007
Graduate School of Life Science, University of Hyogo, 3-2-1 Koto, Kamigori, Hyogo 678-1297, Japan.
We previously demonstrated that hDREF, a human homologue of Drosophila DNA replication-related element binding factor (dDREF), is a DNA-binding protein predominantly distributed with granular structures in the nucleus. Here, glutathione S-transferase pulldown and chemical cross-linking assays showed that the carboxyl-terminal hATC domain of hDREF, highly conserved among hAT transposase family members, possesses self-association activity. Immunoprecipitation analyses demonstrated that hDREF self-associates in vivo, dependent on hATC domain.
View Article and Find Full Text PDFJ Biol Chem
June 2003
Division of Biochemistry, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya 464-8681, Japan.
A human homologue (hDREF/KIAA0785) of Drosophila DREF, a transcriptional regulatory factor required for expression of genes involved in DNA replication and cell proliferation, was identified by BLAST search. Amino acid sequences corresponding to three regions highly conserved between two Drosophila species also proved to be very similar in the hDREF/KIAA0785 polypeptide. A consensus binding sequence (5'-TGTCG(C/T)GA(C/T)A) for hDREF/KIAA0785, determined by the CASTing method, overlapped with that for the Drosophila DREF (5'-TGTCGATA).
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!