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Scientific result | Health ＆ life sciences | DNA | Molecular mechanisms
A team from I2BC has shown, on a genomic scale, that the Mediator of transcription from the yeast S.cerevisiae physically interacts with the chromatin remodeling complex RSC, and that by co-localizing with this complex on DNA promoter regions, it contributes to chromatin organization favorable to transcription initiation.
In eukaryotic cells, DNA is compacted in the form of chromatin, an association of DNA, RNA and proteins, and all associated processes, including the transcription of DNA into messenger RNA, take place in this chromatin context. The Mediator of gene transcription is a large multiprotein complex (1.5 MDa), conserved in eukaryotes, which plays a crucial role in the activation and regulation of transcription by RNA polymerase II. For several years now, Julie Soutourina's team has been investigating the molecular mechanisms involved in the functioning of the Mediator of the yeast Saccharomyces cerevisiae (an eukaryotic model and research tool). It has recently demonstrated a functional interaction between this complex and the nucleotide excision DNA repair mechanism (see Joliot news). In this new work, it investigates the coordination of Mediator functions with another transcription-regulating complex, Remodels the Structure of Chromatin (RSC), which is highly abundant in the cell, conserved and essential for its viability. Here, the researchers show that several Mediator subunits establish physical and functional contact with the RSC, which is involved in the formation of Nucleosome Depleted Regions (NDRs), the eviction of nucleosomes from promoters favoring transcription initiation. The role of the Mediator-RSC interaction in chromatin binding, nucleosome occupancy on DNA and transcription has been determined at the genomic level. The Mediator and RSC co-localize on large NDRs of promoter regions, and Mediator-specific mutations affect nucleosome eviction and stability at the transcription initiation site. This work shows that Mediator of transcription contributes to chromatin remodeling function by shaping nucleosome-depleted DNA regions in gene promoter regions. They will help to understand the importance of transcriptional regulation in the chromatin context relevant to severe diseases. Contact : Julie Soutourina (firstname.lastname@example.org) See also I2BC siteLegend : Involvement of Mediator (MED) in the formation of chromatin remodeler complex (RSC)-dependent nucleosome-depleted regions (NDRs) on DNA promoter regions. André et al., Graphical Abstract, Cell Reports 2023
Kévin M André, Nathalie Giordanengo Aiach, Veronica Martinez-Fernandez, Leo Zeitler, Adriana Alberti, Arach Goldar, Michel Werner, Cyril Denby Wilkes, Julie Soutourina. Functional interplay between Mediator and RSC chromatin remodeling complex controls nucleosome-depleted region maintenance at promoters. Cell Reports, 2023 May 30 ;42(5) :112465 https://doi.org/10.1016/j.celrep.2023.112465
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.