Abstract
BackgroundDia2 is an F-box protein found in the budding yeast, S. cerevisiae. Together with Skp1 and Cul1, Dia2 forms the substrate-determining part of an E3 ubiquitin ligase complex, otherwise known as the SCF. Dia2 has previously been implicated in the control of replication and genome stability via its interaction with the replisome progression complex.Principal FindingsWe identified components of the RSC chromatin remodelling complex as genetic interactors with Dia2, suggesting an additional role for Dia2 in the regulation of transcription. We show that Dia2 is involved in controlling assembly of the RSC complex. RSC belongs to a group of ATP-dependent nucleosome-remodelling complexes that controls the repositioning of nucleosomes. The RSC complex is expressed abundantly and its 17 subunits are recruited to chromatin in response to both transcription activation and repression. In the absence of Dia2, RSC-mediated transcription regulation was impaired, with concomitant abnormalities in nucleosome positioning.ConclusionsOur findings imply that Dia2 is required for the correct assembly and function of the RSC complex. Dia2, by controlling the RSC chromatin remodeller, fine-tunes transcription by controlling nucleosome positioning during transcriptional activation and repression.
Highlights
IntroductionThe RSC complex is the most abundant of such chromatin remodellers in eukaryotes
Our findings imply that Dia2 is required for the correct assembly and function of the RSC complex
(see Figs 1A and 1B for experimental design), we found that deletion of dia2 was synthetically lethal with sth1td, rsc8td and rsc4 td subunits of the RSC complex upon induction of the Ubr1 ubiquitin ligase that targets the degron fusion proteins for destruction, at the semi-permissive temperature of 30 degrees (Fig. 1)
Summary
The RSC complex is the most abundant of such chromatin remodellers in eukaryotes. Comprised of 17 subunits, the RSC complex is an ATP-dependent chromatin remodelling complex that has been demonstrated to slide or disassemble nucleosomes [1,2]. The RSC complex is involved in many other aspects of chromatin metabolism including DNA replication and repair [3,4,5]. In the budding yeast Saccharyomyces cerevisiae, the RSC complex has been shown to bind to transcribed parts of the genome and control nucleosome distribution in response to transcription [6,7]. The RSC complex can exist as sub-modules without the presence of all 17 subunits [8]. Dia has previously been implicated in the control of replication and genome stability via its interaction with the replisome progression complex
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