title: Mediator, SWI/SNF and SAGA complexes regulate Yap8-dependent transcriptional activation of ACR2 in response to arsenate.
abstract: 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.
authors.affiliation: Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.
authors.forename: Regina Andrade
authors.initials: RA
authors.lastname: Menezes
authors.affiliation: Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.
authors.forename: Catarina
authors.initials: C
authors.lastname: Pimentel
authors.affiliation: Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.
authors.forename: Ana Rita Courelas
authors.initials: AR
authors.lastname: Silva
authors.affiliation: Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.
authors.forename: Catarina
authors.initials: C
authors.lastname: Amaral
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR 7238, Laboratoire de Génomique des Microorganismes, F-75005 Paris, France; CNRS, UMR 7238, Laboratoire de Génomique des Microorganismes, F-75005 Paris, France.
authors.forename: Jawad
authors.initials: J
authors.lastname: Merhej
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR 7238, Laboratoire de Génomique des Microorganismes, F-75005 Paris, France; CNRS, UMR 7238, Laboratoire de Génomique des Microorganismes, F-75005 Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Devaux
authors.affiliation: Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal. Electronic address: claudina@itqb.unl.pt.
authors.forename: Claudina
authors.initials: C
authors.lastname: Rodrigues-Pousada
mesh_terms: D053502:Arsenate Reductases / Q000235:genetics* / Q000378:metabolism; D001149:Arsenates / Q000633:toxicity*; D050976:Basic-Leucine Zipper Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D003545:Cysteine / Q000378:metabolism; D056892:Mediator Complex / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological / Q000187:drug effects; D015533:Transcriptional Activation / Q000235:genetics*
chemical_list: C494591:ARR1 protein, S cerevisiae; D001149:Arsenates; D050976:Basic-Leucine Zipper Transcription Factors; D056892:Mediator Complex; D046912:Multiprotein Complexes; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; C506971:ARR2 protein, S cerevisiae; D053502:Arsenate Reductases; D003545:Cysteine; C025657:arsenic acid
keywords: ACR2; Mediator; SAGA; SWI/SNF; Yap8