Independent Recruitment of Mediator and SAGA by the Activator Met4

Abstract

Mediator is a key RNA polymerase II (Pol II) cofactor in the regulation of eukaryotic gene expression. It is believed to function as a coactivator linking gene-specific activators to the basal Pol II initiation machinery. In support of this model, we provide evidence that Mediator serves in vivo as a coactivator for the yeast activator Met4, which controls the gene network responsible for the biosynthesis of sulfur-containing amino acids and S-adenosylmethionine. In addition, we show that SAGA (Spt-Ada-Gcn5-acetyltransferase) is also recruited to Met4 target promoters, where it participates in the recruitment of Pol II by a mechanism involving histone acetylation. Interestingly, we find that SAGA is not required for Mediator recruitment by Met4 and vice versa. Our results provide a novel example of functional interplay between Mediator and coactivators involved in histone modification.

Supplemental material for this article may be found at http://mcb.asm.org/.

We are grateful to Dominique Thomas for constant support and critical reading of the manuscript. We thank Rick Young, Young Chul Lee, and Franklin Pugh for strains.

This work was supported by funds from the Centre National de la Recherche Scientifique and grants to L.K. from the Ministère de la Recherche (ACI Jeune Chercheur 2001) and the Association pour la Recherche sur le Cancer (subvention ARC no. 3578). C.L. was supported in part by a fellowship from the Ligue Nationale contre le Cancer.