CGM - Department Genes Expression

Transcriptional regulation in yeast

Group leader: Laurent KURAS

  Last update: 14-Oct-2011

• Our team
• Our address
• Research themes
• Selected publications

 

Our team

Our address

Research themes

Regulation of gene expression involves hundreds of transcription activators each recognizing and activating transcription of specific subsets of genes. Activators function by stimulating assembly and activity of the transcription initiation machinery comprising RNA polymerase II and the general transcription factors IIB, IID, IIE, IIF and IIH (see Figure 1). In current models, activators are supposed to operate through coactivators, even though direct contacts with the transcription initiation machinery are not excluded. Two major types of coactivators exist: those that act on the structure of chromatin, either by changing the position of nucleosomes or by posttranslational modification of nucleosomal histones; and those that act directly on the transcription initiation machinery, such as Mediator of transcription or TBP associated factors (TAF) within TFIID.

Our research uses the budding yeast Saccharomyces cerevisiae as a model organism and aims at a better understanding of the mechanisms of transcription activation, including how activators operate and how they are regulated in response to the environmental conditions.

One facet of our work concerns Mediator of transcription, a protein complex comprising more than 20 subunits discovered in the early 1990s in yeast and found afterwards in mammals and human. It is now established that Mediator is a coactivator of first importance essential for the proper functioning of the cell. However, a number of key questions remains unresolved concerning the exact role of Mediator in transcription regulation and how it contributes to the assembly and activity of the transcription initiation machinery. Our research addresses these questions by taking advantage of the possibilities offered by the budding yeast at the level of genetics, molecular biology and functional genomics.

Another facet of our work concerns the regulation of the gene network controlling in yeast biosynthesis of the sulfur-containing amino acids methionine and cysteine. This network (called MET network) comprises 20 genes spread throughout the genome, whose transcription is regulated depending on the sulfur status. We use the MET network as model system to study the molecular mechanisms by which eukaryotic cells can achieve coordinated regulation of genes involved in a biological pathway. We already know that activation of the MET network involves an activator, Met4, and four auxiliary DNA-binding cofactors, Cbf1, Met28, Met31 and Met32 (see Figure 2). We also know that Met4 activity is regulated by ubiquitylation through the SCF^Met30 ubiquitin-ligase. Our present research focuses on the coactivators involved in the regulation of the MET network, especially the coactivators affecting the chromatin structuree.

Selected publications