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 (julie.soutourina@cea.fr)
See also I2BC site
Legend : 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
- Remodels the Structure of Chromatin (RSC) : The chromatin structure of DNA is an obstacle to gene transcription, as it limits the accessibility of DNA promoters, the sites of transcription initiation. Specialized complexes, such as RSC, are capable of remodeling this structure, thereby helping to control gene expression. Their role is essential, since mutations in the human homologue of RSC are responsible for 20% of cancers.
- The nucleosome is the basic unit of chromatin organization. It consists of a DNA segment of 146 or 147 nucleotide pairs, wrapped around a core of histone proteins.