Cooperativity of Stress-Responsive Transcription Factors in Core Hypoxia-Inducible Factor Binding Regions

Diego Villar, Amaya Ortiz-Barahona, Laura Gómez-Maldonado, Nuria Pescador, Fátima Sánchez-Cabo, Hubert Hackl, Benjamin A T Rodriguez, Zlatko Trajanoski, Ana Dopazo, Hui-ming Huang, Pearlly S. Yan, Luis del Peso

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The transcriptional response driven by Hypoxia-inducible factor (HIF) is central to the adaptation to oxygen restriction. Despite recent characterization of genome-wide HIF DNA binding locations and hypoxia-regulated transcripts in different cell types, the molecular bases of HIF target selection remain unresolved. Herein, we combined multi-level experimental data and computational predictions to identify sequence motifs that may contribute to HIF target selectivity. We obtained a core set of bona fide HIF binding regions by integrating multiple HIF1 DNA binding and hypoxia expression profiling datasets. This core set exhibits evolutionarily conserved binding regions and is enriched in functional responses to hypoxia. Computational prediction of enriched transcription factor binding sites identified sequence motifs corresponding to several stress-responsive transcription factors, such as activator protein 1 (AP1), cAMP response element-binding (CREB), or CCAAT-enhancer binding protein (CEBP). Experimental validations on HIF-regulated promoters suggest a functional role of the identified motifs in modulating HIF-mediated transcription. Accordingly, transcriptional targets of these factors are over-represented in a sorted list of hypoxia-regulated genes. Altogether, our results implicate cooperativity among stress-responsive transcription factors in fine-tuning the HIF transcriptional response.

Original languageEnglish (US)
Article numbere45708
JournalPLoS One
Volume7
Issue number9
DOIs
StatePublished - Sep 24 2012
Externally publishedYes

Fingerprint

hypoxia
Transcription Factors
transcription factors
Genes
CCAAT-Enhancer-Binding Proteins
Transcription factors
DNA
Transcription Factor AP-1
Response Elements
Tuning
Binding Sites
Oxygen
Hypoxia
prediction
response elements
binding proteins
binding sites
transcription (genetics)
promoter regions
Genome

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Villar, D., Ortiz-Barahona, A., Gómez-Maldonado, L., Pescador, N., Sánchez-Cabo, F., Hackl, H., ... del Peso, L. (2012). Cooperativity of Stress-Responsive Transcription Factors in Core Hypoxia-Inducible Factor Binding Regions. PLoS One, 7(9), [e45708]. https://doi.org/10.1371/journal.pone.0045708

Cooperativity of Stress-Responsive Transcription Factors in Core Hypoxia-Inducible Factor Binding Regions. / Villar, Diego; Ortiz-Barahona, Amaya; Gómez-Maldonado, Laura; Pescador, Nuria; Sánchez-Cabo, Fátima; Hackl, Hubert; Rodriguez, Benjamin A T; Trajanoski, Zlatko; Dopazo, Ana; Huang, Hui-ming; Yan, Pearlly S.; del Peso, Luis.

In: PLoS One, Vol. 7, No. 9, e45708, 24.09.2012.

Research output: Contribution to journalArticle

Villar, D, Ortiz-Barahona, A, Gómez-Maldonado, L, Pescador, N, Sánchez-Cabo, F, Hackl, H, Rodriguez, BAT, Trajanoski, Z, Dopazo, A, Huang, H, Yan, PS & del Peso, L 2012, 'Cooperativity of Stress-Responsive Transcription Factors in Core Hypoxia-Inducible Factor Binding Regions', PLoS One, vol. 7, no. 9, e45708. https://doi.org/10.1371/journal.pone.0045708
Villar D, Ortiz-Barahona A, Gómez-Maldonado L, Pescador N, Sánchez-Cabo F, Hackl H et al. Cooperativity of Stress-Responsive Transcription Factors in Core Hypoxia-Inducible Factor Binding Regions. PLoS One. 2012 Sep 24;7(9). e45708. https://doi.org/10.1371/journal.pone.0045708
Villar, Diego ; Ortiz-Barahona, Amaya ; Gómez-Maldonado, Laura ; Pescador, Nuria ; Sánchez-Cabo, Fátima ; Hackl, Hubert ; Rodriguez, Benjamin A T ; Trajanoski, Zlatko ; Dopazo, Ana ; Huang, Hui-ming ; Yan, Pearlly S. ; del Peso, Luis. / Cooperativity of Stress-Responsive Transcription Factors in Core Hypoxia-Inducible Factor Binding Regions. In: PLoS One. 2012 ; Vol. 7, No. 9.
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