Cooperation between SAGA and SWI/SNF complexes is required for efficient transcriptional responses regulated by the yeast MAPK Slt2

Abstract

The transcriptional response of Saccharomyces cerevisiae to cell wall stress is mainly mediated by the cell wall integrity (CWI) pathway through the MAPK Slt2 and the transcription factor Rlm1. Once activated, Rlm1 interacts with the chromatin remodeling SWI/SNF complex which locally alters nucleosome positioning at the target promoters. Here we show that the SAGA complex plays along with the SWI/SNF complex an important role for eliciting both early induction and sustained gene expression upon stress. Gcn5 co-regulates together with Swi3 the majority of the CWI transcriptional program, except for a group of genes which are only dependent on the SWI/SNF complex. SAGA subunits are recruited to the promoter of CWI-responsive genes in a Slt2, Rlm1 and SWI/SNF-dependent manner. However, Gcn5 mediates acetylation and nucleosome eviction only at the promoters of the SAGA-dependent genes. This process is not essential for pre-initiation transcriptional complex assembly but rather increase the extent of the remodeling mediated by SWI/SNF. As a consequence, H3 eviction and Rlm1 recruitment is completely blocked in a swi3Δ gcn5Δ double mutant. Therefore, SAGA complex, through its histone acetylase activity, cooperates with the SWI/SNF complex for the mandatory nucleosome displacement required for full gene expression through the CWI pathway.

Flocculation of Saccharomyces cerevisiae is dependent on activation of Slt2 and Rlm1 regulated by the cell wall integrity pathway

“…The epigenetic and genetic factors induce structural and chemical changes in the chromatin, impacting the expression of responsive genes. Upon cell wall stress, S. cerevisiae activates an adaptive transcriptional response to counterbalance the stress, mediated by the Slt2‐dependent MAPK signaling pathway (Sanz et al , ; Sanz et al , ; García et al , ). Flocculation of yeast cells is another mechanism which provides adaptation to several types of extrinsic and intrinsic stress conditions including cell wall stress (Cheng et al , ).…”

“…In response to cell wall stressors, the Slt2 MAPK, binds and activates its transcription factors; SBF (SCB‐binding factor) and Rlm1 (Sanz et al , ). Phosphorylation of these transcription factors by Slt2 triggers the recruitment of transcriptional machinery at their target genes (Sanz et al , ). Dual specificity protein phosphatases Msg5 or Sdp1 act as negative regulators of Slt2 (Liu and Levin, ), and maintain the Slt2 at low activity state in the absence of stress (Martı́n et al , ).…”

SWI/SNF coordinates transcriptional activation through Rpd3-mediated histone hypoacetylation during quiescence entry

“…Additionally, SWI/SNF specifically displaces nucleosomes acetylated by SAGA (Chandy et al, 2006;Hassan et al, 2006;Hassan et al, 2002). Histone acetylation also regulates the chromatin remodeling activity of SWI/SNF at stress response genes such as those in the Slt2 MAPK pathway (Sanz et al, 2012;Sanz et al, 2016), the heat shock response (Shivaswamy and Iyer, 2008), and the response to low glucose (Dutta et al, 2014).…”

A novel link between Cell Wall Integrity pathway and Flocculation, regulated by yeast Sen1 dependent interplay between Rlm1 and Tup1

“…For example; the transcriptional induction of one of the CWI genes occurs in response to cell wall damage through the Slt2 activation-dependent recruitment of Rlm1, SWI2/SNF2 and SAGA complexes (SANZ et al 2012;SANZ et al 2016). Under non-inducing conditions, transcription of CWI genes is terminated by the binding of Nrd1-Nab3-Sen1 (NNS) complex.…”