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Mediator, SWI/SNF and SAGA complexes regulate Yap8-dependent transcriptional activation of ACR2 in response to arsenate.

TitleMediator, SWI/SNF and SAGA complexes regulate Yap8-dependent transcriptional activation of ACR2 in response to arsenate.
Publication TypeJournal Article
Year of Publication2017
AuthorsMenezes, RAndrade, Pimentel, C, Silva, ARita Coure, Amaral, C, Merhej, J, Devaux, F, Rodrigues-Pousada, C
JournalBiochim Biophys Acta
Date Published2017 04
KeywordsArsenate Reductases, Arsenates, Basic-Leucine Zipper Transcription Factors, Cysteine, Mediator Complex, Multiprotein Complexes, Promoter Regions, Genetic, Protein Binding, Protein Subunits, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Stress, Physiological, Transcriptional Activation

Response to arsenic stress in Saccharomyces cerevisiae is orchestrated by the regulatory protein Yap8, which mediates transcriptional activation of ACR2 and ACR3. This study contributes to the state of art knowledge of the molecular mechanisms underlying yeast stress response to arsenate as it provides the genetic and biochemical evidences that Yap8, through cysteine residues 132, 137, and 274, is the sensor of presence of arsenate in the cytosol. Moreover, it is here reported for the first time the essential role of the Mediator complex in the transcriptional activation of ACR2 by Yap8. Based on our data, we propose an order-of-function map to recapitulate the sequence of events taking place in cells injured with arsenate. Modification of the sulfhydryl state of these cysteines converts Yap8 in its activated form, triggering the recruitment of the Mediator complex to the ACR2/ACR3 promoter, through the interaction with the tail subunit Med2. The Mediator complex then transfers the regulatory signals conveyed by Yap8 to the core transcriptional machinery, which culminates with TBP occupancy, ACR2 upregulation and cell adaptation to arsenate stress. Additional co-factors are required for the transcriptional activation of ACR2 by Yap8, particularly the nucleosome remodeling activity of SWI/SNF and SAGA complexes.

Alternate JournalBiochim. Biophys. Acta
PubMed ID28188921

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