Dataset Information

Functional and topological characterization of transcriptional cooperativity in yeast.

ABSTRACT:

Background

Many cellular programs are regulated through the integration of specific transcriptional signals originated from external stimuli, being cooperation between transcription factors a key feature in this process. In this work, we studied how transcriptional cooperativity in yeast is aimed at integrating different regulatory inputs rather than controlling particular cellular functions from a organizational, evolutionary and functional point of view.

Findings

Our results showed that cooperative transcription factor pairs co-evolve and are essential for the life of the cell. When organized into a layered regulatory network, we observed that cooperative transcription factors were preferentially placed in the middle layers, which highlights a role in regulatory signal integration. We also observed significant co-activity and co-evolution between members of the same cooperative pairs, but a lack of common co-expression profile.

Conclusions

Our results suggest that transcriptional cooperativity has a specific role within the regulatory control scheme of the cell, focused in the amplification and integration of cellular signals rather than control of particular cellular functions. This information can be used for better characterization of regulatory interactions between transcription factors, aimed at determining the spatial and temporal control of gene expression.

SUBMITTER: Aguilar D

PROVIDER: S-EPMC3499397 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Publications

Functional and topological characterization of transcriptional cooperativity in yeast.

Aguilar Daniel D Oliva Baldo B

BMC research notes 20120510

<h4>Background</h4>Many cellular programs are regulated through the integration of specific transcriptional signals originated from external stimuli, being cooperation between transcription factors a key feature in this process. In this work, we studied how transcriptional cooperativity in yeast is aimed at integrating different regulatory inputs rather than controlling particular cellular functions from a organizational, evolutionary and functional point of view.<h4>Findings</h4>Our results sho ...[more]

PMID: 22574744

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Project description:The glucokinase gene GLK1 of the yeast Saccharomyces cerevisiae is transcriptionally regulated in response to the carbon source of the growth medium. Northern-blot analysis shows that the GLK1 gene is expressed at a basal level in the presence of glucose, de-repressed more than 6-fold under conditions of sugar limitation and more than 25-fold under conditions of ethanol induction. lacZ fusions of the GLK1 gene promoter were constructed and a deletion analysis was performed in order to identify the cis-acting regulatory elements of the promoter that controls GLK1 gene expression. First, the expression seemed to be mediated mainly by one GCR1 and three stress-responsive element (STRE) activating elements. Secondly, an ethanol repression autoregulation (ERA)/twelve-fold TA repeat (TAB) repressor element was identified within the promoter region of the GLK1 gene. A specific and differential protein binding to the STRE was observed with extracts from de-repressed and repressed cells. No differential binding to the GCR1 or ERA/TAB elements was observed with extracts from de-repressed and repressed cells, but, in both cases, the binding was competed for by an excess of the unlabelled GLK1(GCR1) and GLK1(ERA) sequence. The transcription factors Msn2 and Msn4, which bind to the GLK1 upstream region through the STRE, contribute to inductive activation. The transcription factor Gcr1, which binds through the GCR1 element, contributes to constitutive activation. In order to achieve the severe glucose repression of GLK1, constitutive repressor factors acting through the ERA/TAB element must counteract constitutive activation generated by Gcr1 binding to the GCR1 element. Full expression of the GLK1 gene is produced by inductive activation of three STRE when Msn2 and Msn4 proteins are translocated to the nucleus by covalent modification. The combinatorial effect of the entire region leads to the regulated transcription of GLK1, i.e., silent in media with glucose and other preferred carbon sources, such as fructose or mannose, and increased levels of expression upon glucose depletion.

Dataset Information

Functional and topological characterization of transcriptional cooperativity in yeast.

Background

Findings

Conclusions

Publications

Functional and topological characterization of transcriptional cooperativity in yeast.

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