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The transcription factor Ifh1 is a key regulator of yeast ribosomal protein genes

Nature volume 432, pages 1054–1058 (2004)Cite this article

Abstract

Ribosomal protein (RP) genes in eukaryotes are coordinately regulated in response to growth stimuli and environmental stress, thereby permitting cells to adjust ribosome number and overall protein synthetic capacity to physiological conditions1,2,3,4,5. Approximately 50% of RNA polymerase II transcription is devoted to RP genes5. The transcriptional regulator Rap1 binds most yeast RP promoters6, and Rap1 sites are important for coordinate regulation of RP genes7,8,9,10. However, Rap1 is not the specific regulator that controls RP transcription because it also functions as a repressor, and many Rap1-activated promoters are not coordinately regulated with RP promoters11,12. Here we show that the transcription factors Fhl1 and Ifh1 associate almost exclusively with RP promoters; association depends on Rap1 and (to a lesser extent) a DNA element at many RP promoters. Ifh1 is recruited to promoters via the forkhead-associated (FHA) domain of Fhl1; the level of Ifh1 associated with RP promoters determines the level of transcription; and environmental stress causes a marked reduction in the association of Ifh1, but not Fhl1 or Rap1. Thus, Ifh1 association with promoters is the key regulatory step for coordinate expression of RP genes.

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Figure 1: Promoter-specificity of Fhl1 and Ifh1.
Figure 2: Role of the Rap1 site and the IFHL motif.
Figure 3: Ifh1-dependent induction of transcription at Ifh1-bound RP genes.
Figure 4: Effect of environmental stress on transcription and binding of Rap1, Fhl1 and Ifh1.

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Acknowledgements

We thank D. Shore for communicating similar results before publication, N. Reppas for help with computational analysis, J. Weiner for assistance with microarrays, and F. Bachand, C. Baisden, and Z. Moqtaderi for technical assistance. We thank J. Geisberg, P. Mason and Z. Moqtaderi for discussions. J.T.W. was supported by a long-term EMBO fellowship, and D.B.H. was supported by a Helen Hay Whitney postdoctoral fellowship. This work was supported by grants to K.S. from the National Institutes of Health.

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Authors and Affiliations

  1. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, 02115, USA

    Joseph T. Wade, Daniel B. Hall & Kevin Struhl

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  1. Joseph T. Wade
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Correspondence to Kevin Struhl.

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Supplementary information

Supplementary Figure 1

Motifs identified from Fhl1 and Ifh1 ChIP-chip analyses. a. Rap1 DNA site as derived from the RP gene promoters identified as Fhl1 targets by ChIP-chip analysis. b. A-rich stretch as derived from the RP gene promoters identified as Fhl1 targets by ChIP-chip analysis. c. Rap1 DNA site as derived from the RP gene promoters identified as Ifh1 targets by ChIP-chip analysis. d. A-rich stretch as derived from the RP gene promoters identified as Ifh1 targets by ChIP-chip analysis. e. IFHL motif as derived from the RP gene promoters identified as Ifh1 targets by ChIP-chip analysis. f. Motif 213 as described previously (Beer and Tavazoie, 2004). (JPG 72 kb)

Supplementary Figure 2

Rap1 occupancy is unaffected by Ifh1 expression. Occupancy of Rap1 0, 30 and 60 min after galactose addition in a strain expressing plasmid-borne copy of IFH1 under the control of the GAL1 promoter. (JPG 37 kb)

Supplementary Figure 3

Effect of heat shock on occupancy of Gal4 fusions. Occupancy of Gal4 DBD, Gal4-FHA and Gal4-Gcr2 at the GAL7 promoter before and after a heat shock. (JPG 31 kb)

Supplementary Table 1

Microarray data for Fhl1 and Ifh1 ChIP-chip. (XLS 1810 kb)

Supplementary Data

MIAME Checklist. (DOC 21 kb)

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Wade, J., Hall, D. & Struhl, K. The transcription factor Ifh1 is a key regulator of yeast ribosomal protein genes. Nature 432, 1054–1058 (2004). https://doi.org/10.1038/nature03175

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