Transcription Factor hDREF Is a Novel SUMO E3 Ligase of Mi2?.

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 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.

SUBMITTER: Yamashita D 

PROVIDER: S-EPMC4882432 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature