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Genetic reconstruction of a functional transcriptional regulatory network

Nature Genetics volume 39, pages 683–687 (2007)Cite this article

Abstract

Although global analyses of transcription factor binding provide one view of potential transcriptional regulatory networks1,2, regulation also occurs at levels distinct from transcription factor binding3,4. Here, we use a genetic approach to identify targets of transcription factors in yeast and reconstruct a functional regulatory network. First, we profiled transcriptional responses in S. cerevisiae strains with individual deletions of 263 transcription factors. Then we used directed-weighted graph modeling and regulatory epistasis analysis to identify indirect regulatory relationships between these transcription factors, and from this we reconstructed a functional transcriptional regulatory network. The enrichment of promoter motifs and Gene Ontology annotations provide insight into the biological functions of the transcription factors.

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Figure 1: Validation of the transcription factor deletion strains and expression profiling data.
Figure 2: Regulatory epistasis analysis and functional network refinement.
Figure 3: Overlap between transcription factor–regulated targets and binding targets.
Figure 4: Enrichment of sequence motifs and biological impact of transcription factor deletions.

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Acknowledgements

We thank members of the Iyer lab for help with microarray printing; T. Hughes, B. Ren, H. Dai and M. Robinson for advice on the error model; E. Marcotte for discussions and suggestions and J. Gu for statistical advice. This work was supported by grants from the US National Institutes of Health (NIH) and the US National Science Foundation (V.R.I.), by a training grant from the US National Institute on Alcohol Abuse and Alcoholism and by a University of Texas Continuing Fellowship (P.J.K.).

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Author notes

  1. Zhanzhi Hu

    Present address: Current address: Dental Research Institute, University of California at Los Angeles, Los Angeles, California 90095-1668, USA.,

  2. Zhanzhi Hu and Patrick J Killion: These authors contributed equally to this work.

Authors and Affiliations

  1. Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, University of Texas at Austin, 1 University Station A4800, Austin, 78712, Texas, USA

    Zhanzhi Hu, Patrick J Killion & Vishwanath R Iyer

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  1. Zhanzhi Hu
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  2. Patrick J Killion
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  3. Vishwanath R Iyer
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Contributions

Z.H., P.J.K. and V.R.I. designed the study, Z.H. did the microarray experiments, P.J.K. wrote the software, P.J.K. and Z.H. did the analysis and wrote the supplementary information and Z.H. and V.R.I. wrote the manuscript.

Note: Supplementary information is available on the Nature Genetics website.

Corresponding author

Correspondence to Vishwanath R Iyer.

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Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Significance values of transcription factor targets. (PDF 108 kb)

Supplementary Table 1

Saccharomyces cerevisiae strain information. (PDF 117 kb)

Supplementary Table 2

ChIP-chip and TF knockout target overlap analysis. (PDF 50 kb)

Supplementary Table 3

Results of motif analysis. (XLS 107 kb)

Supplementary Table 4

Results of Gene Ontology analysis. (XLS 1128 kb)

Supplementary Table 5

RNA-binding proteins. (PDF 104 kb)

Supplementary Table 6

HSF1-based post-binding regulatory analysis results. (PDF 60 kb)

Supplementary Methods (PDF 204 kb)

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Hu, Z., Killion, P. & Iyer, V. Genetic reconstruction of a functional transcriptional regulatory network. Nat Genet 39, 683–687 (2007). https://doi.org/10.1038/ng2012

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