Ixr1p from Saccharomyces cerevisiae has been previously studied because it binds to DNA containing intrastrand cross-links formed by the anticancer drug cisplatin. Ixr1p is also a transcriptional regulator of anaerobic/hypoxic genes, such as SRP1/TIR1, which encodes a stress-response cell wall manoprotein, and COX5B, which encodes the Vb subunit of the mitochondrial complex cytochrome c oxidase. However, factors controlling IXR1 expression remained unexplored. In the present study we show that IXR1 mRNA levels are controlled by oxygen availability and increase during hypoxia. In aerobiosis, low levels of IXR1 expression are maintained by Rox1p repression through the general co-repressor complex Tup1–Ssn6. Ixr1p itself is necessary for full IXR1 expression under hypoxic conditions. Deletion analyses have identified the region in the IXR1 promoter responsible for this positive auto-control (nucleotides −557 to −376). EMSA (electrophoretic mobility-shift assay) and ChIP (chromatin immunoprecipitation) assays show that Ixr1p binds to the IXR1 promoter both in vitro and in vivo. Ixr1p is also required for hypoxic repression of ROX1 and binds to its promoter. UPC2 deletion has opposite effects on IXR1 and ROX1 transcription during hypoxia. Ixr1p is also necessary for resistance to oxidative stress generated by H2O2. IXR1 expression is moderately activated by H2O2 and this induction is Yap1p-dependent. A model of IXR1 regulation as a relay for sensing different signals related to change in oxygen availability is proposed. In this model, transcriptional adaptation from aerobiosis to hypoxia depends on ROX1 and IXR1 cross-regulation.
Skip Nav Destination
Article navigation
January 2010
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
December 14 2009
Regulatory factors controlling transcription of Saccharomyces cerevisiae IXR1 by oxygen levels: a model of transcriptional adaptation from aerobiosis to hypoxia implicating ROX1 and IXR1 cross-regulation
Raquel Castro-Prego;
Raquel Castro-Prego
1
1Departamento de Biología Celular y Molecular, Facultad de Ciencias, Universidad de A Coruña, 15071, Spain
Search for other works by this author on:
Mónica Lamas-Maceiras;
Mónica Lamas-Maceiras
1Departamento de Biología Celular y Molecular, Facultad de Ciencias, Universidad de A Coruña, 15071, Spain
Search for other works by this author on:
Pilar Soengas;
Pilar Soengas
1Departamento de Biología Celular y Molecular, Facultad de Ciencias, Universidad de A Coruña, 15071, Spain
Search for other works by this author on:
Isabel Carneiro;
Isabel Carneiro
1Departamento de Biología Celular y Molecular, Facultad de Ciencias, Universidad de A Coruña, 15071, Spain
Search for other works by this author on:
Isabel González-Siso;
Isabel González-Siso
1Departamento de Biología Celular y Molecular, Facultad de Ciencias, Universidad de A Coruña, 15071, Spain
Search for other works by this author on:
M. Esperanza Cerdán
M. Esperanza Cerdán
2
1Departamento de Biología Celular y Molecular, Facultad de Ciencias, Universidad de A Coruña, 15071, Spain
2To whom correspondence should be addressed (email bmanamrt@udc.es).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
September 28 2009
Accepted:
October 06 2009
Accepted Manuscript online:
October 06 2009
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2010 Biochemical Society
2010
Biochem J (2010) 425 (1): 235–243.
Article history
Received:
September 28 2009
Accepted:
October 06 2009
Accepted Manuscript online:
October 06 2009
Citation
Raquel Castro-Prego, Mónica Lamas-Maceiras, Pilar Soengas, Isabel Carneiro, Isabel González-Siso, M. Esperanza Cerdán; Regulatory factors controlling transcription of Saccharomyces cerevisiae IXR1 by oxygen levels: a model of transcriptional adaptation from aerobiosis to hypoxia implicating ROX1 and IXR1 cross-regulation. Biochem J 1 January 2010; 425 (1): 235–243. doi: https://doi.org/10.1042/BJ20091500
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.