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Structure and function of a transcriptional network activated by the MAPK Hog1

Abstract

Cells regulate gene expression using a complex network of signaling pathways, transcription factors and promoters. To gain insight into the structure and function of these networks, we analyzed gene expression in single- and multiple-mutant strains to build a quantitative model of the Hog1 MAPK-dependent osmotic stress response in budding yeast. Our model reveals that the Hog1 and general stress (Msn2/4) pathways interact, at both the signaling and promoter level, to integrate information and create a context-dependent response. This study lays out a path to identifying and characterizing the role of signal integration and processing in other gene regulatory networks.

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Figure 1: Single- and double-mutant analysis of gene expression.
Figure 2: Role of Hog1 and Msn2/4 in osmotic stress–dependent gene induction.
Figure 3: Mechanism of Hog1-dependent gene activation.
Figure 4: ChIP analysis of Sko1 and Hot1 binding sites.
Figure 5: Structure of the transcriptional network activated by the MAPK Hog1.
Figure 6: Context-dependent gene activation by the Hog1–Msn2/4 network.

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Gene Expression Omnibus

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Acknowledgements

We thank D. Steger, D. Wykoff, A. Carroll and C. Hopkins from Agilent for advice regarding microarray, ChIP and other procedures; T. Lee and R. Young for sharing their tiling-array design and hybridization protocol before publication; H. Margalit and members of the O'Shea, Friedman and Regev laboratories for helpful discussions; and P. Grosu for help with Rosetta Resolver. We are also grateful to E. Lander, D. Pe'er, D. Koller, R. Losick, M. Brenner and B. Stern for reading the manuscript before publication. A.P.C. was a Howard Hughes Medical Institute (HHMI) Fellow of the Life Sciences Research Foundation and A.R. was supported by a Career Award at the Scientific Interface from the Burroughs Wellcome Fund. This work was supported by HHMI (E.K.O.) and a grant from the Human Frontiers Science Program (E.K.O., A.R. and N.F.).

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Correspondence to Erin K O'Shea.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–8, Supplementary Note and Supplementary Methods (PDF 1905 kb)

Supplementary table 1

Raw data for KCl stress and YEPD experiments (XLS 9579 kb)

Supplementary table 2

Expression component data for KCl experiments (gene in Hog1 network) (XLS 200 kb)

Supplementary table 3

Expression component data for KCl experiments (all genes) (XLS 16376 kb)

Supplementary table 4

Raw data for glucose experiments (XLS 1889 kb)

Supplementary table 5

Expression component data for glucose experiments (all genes) (XLS 2122 kb)

Supplementary table 6

List of strains used in this study (XLS 39 kb)

Supplementary table 7

Microscopy images and data (XLS 5256 kb)

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Capaldi, A., Kaplan, T., Liu, Y. et al. Structure and function of a transcriptional network activated by the MAPK Hog1. Nat Genet 40, 1300–1306 (2008). https://doi.org/10.1038/ng.235

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  • DOI: https://doi.org/10.1038/ng.235

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