Reference: Menezes RA, et al. (2017) Mediator, SWI/SNF and SAGA complexes regulate Yap8-dependent transcriptional activation of ACR2 in response to arsenate. Biochim Biophys Acta Gene Regul Mech 1860(4):472-481

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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.

Reference Type
Journal Article | Research Support, Non-U.S. Gov't
Authors
Menezes RA, Pimentel C, Silva AR, Amaral C, Merhej J, Devaux F, Rodrigues-Pousada C
Primary Lit For
MED2 | ARR1 | ARR2 | ARR3 | SWI/SNF chromatin remodelling complex | Core mediator complex | SAGA complex
Additional Lit For
UFD2

Regulation Annotations 2 entries for 3 genes


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RegulatorTargetDirectionRegulation OfHappens DuringMethodEvidence
ARR1ARR2positivetranscriptioncellular response to arsenic-containing substancemanually curatedquantitative reverse transcription polymerase chain reaction evidence
ARR1ARR3transcriptionmanually curatedchromatin immunoprecipitation-chip evidence
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Interaction Annotations


Genetic Interactions

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Interactor Interactor Allele Assay Annotation Action Phenotype SGA score P-value Source Reference

Physical Interactions 2 entries for 2 genes

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InteractorInteractorAssayAnnotationActionModification
MED2ARR1Two-hybridmanually curatedHit-BaitNo Modification
MED2ARR1Affinity Capture-Westernmanually curatedHit-BaitNo Modification
Showing 1 to 2 of 2 entries