Sus1 Modulates Chromatin Remodeling and Gene Expression via the Cell Wall Integrity Pathway in Saccharomyces...

Stressful situations that compromise the integrity of the fungal cell wall activate a transcriptional reprogramming mainly regulated by the MAPK Slt2 and the transcription factor Rlm1. Chromatin remodeling during this response involves the coordinated action of the SAGA complex, through its histone acetyltransferase Gcn5, and the SWI/SNF complex. Here, we define the specific contribution of another SAGA subunit, Sus1, which is also part of the TREX-2 complex and the deubiquitinating module, in this process. Deleting SUS1 has a widespread impact on the transcriptional program controlled by the cell wall integrity (CWI) pathway. During cell wall stress, Sus1 associates with CWI-responsive genes as part of the SAGA complex through a mechanism involving Slt2, Rlm1, SWI/SNF, and SAGA itself. This association facilitates pre-initiation complex assembly and RNA Pol II progression. Loss of Sus1 reduces histone H3 eviction and nucleosome displacement at CWI-dependent genes under stress. Notably, this function is independent of histone H2B deubiquitination catalyzed by Ubp8. Moreover, the double sus1Δ gcn5Δ mutant exhibits additive effects on chromatin remodeling of CWI-dependent genes under stress and on cell wall stress-related phenotypes, indicating that Sus1 plays a direct role in this remodeling, acting via the CWI pathway independently of Gcn5-mediated histone acetylation. These findings highlight a functional cooperation between Sus1 and Gcn5 in promoting transcriptional activation under stress and reveal new insights into the modular regulation of the SAGA complex during adaptive responses in fungi.