Distinct role of Mediator tail module in regulation of SAGA-dependent, TATA-containing genes in yeast

Abstract

The evolutionarily conserved Mediator complex is required for transcription of nearly all RNA Pol II‐dependent promoters, with the tail module serving to recruit Mediator to active promoters in current models. However, transcriptional dependence on tail module subunits varies in a gene‐specific manner, and the generality of the tail module requirement for transcriptional activation has not been explored. Here, we show that tail module subunits function redundantly to recruit Mediator to promoters in yeast, and transcriptome analysis shows stronger effects on genome‐wide expression in a double‐tail subunit deletion mutant than in single‐subunit deletion mutants. Unexpectedly, TATA‐containing and SAGA‐dependent genes were much more affected by impairment of tail module function than were TFIID‐dependent genes. Consistent with this finding, Mediator and preinitiation complex association with SAGA‐dependent promoters is substantially reduced in gal11/med15Δ med3Δ yeast, whereas association of TBP, Pol II, and other Mediator modules with TFIID‐dependent genes is largely independent of the tail module. Thus, we have identified a connection between the Mediator tail module and the division of promoter dependence between TFIID and SAGA.

Suppression of Mediator is regulated by Cdk8-dependent Grr1 turnover of the Med3 coactivator

“…1C, black bars) were both occupied by Med3. This observation is consistent with the requirement for Med3 in the establishment of a stable preinitiation complex (14,15) and its role in the recruitment of core Mediator (7,11).…”

“…1A). This mode of SAGA-dependent Mediator-regulated activation of gene expression is one of two modalities that have emerged for transcription involving these two regulatory complexes (15).…”

Selective role of Mediator tail module in the transcription of highly regulated genes in yeast

“…9 In contrast, the tail module contains only non-essential subunits and deletion of any individual tail module subunit affects the expression of only a fraction of the genome, 4,5 indicating that the tail module has a gene selective rather than a general role in transcription. The question then arises as to which genes require the tail module for their expression.…”

“…15,16 Consistent with the strong correlation that we found between SAGA dependent and tail module dependent genes, we observed significant enrichment of general stress response genes among genes affected by loss of tail module subunits. 5 The tail module therefore seems to act as a global transcriptional co-activator of stress response genes. In contrast, deletion of kinase module subunits Cdk8/ Srb10 and Med12/Srb8 causes upregulation of many of these same stress response genes.…”

“…The yeast Mediator tail module comprises Med2, Med3, Med15/Gal11 and Med16/ Sin4 subunits, and microarray experiments together with biochemical data indicate that Med2, Med3 and Med15/Gal11 belong to a functionally discrete submodule. 4,5 (A new nomenclature for Mediator subunits was adopted in 2004, 6 so some subunits have more than one name). [7][8][9][10] while in mammals, SREBP-1 interacts with Med15.…”