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Gene loops juxtapose promoters and terminators in yeast

Nature Genetics volume 36, pages 1014–1018 (2004)Cite this article

Abstract

Mechanistic analysis of transcriptional initiation and termination by RNA polymerase II (PolII) indicates that some factors are common to both processes1,2. Here we show that two long genes of Saccharomyces cerevisiae, FMP27 and SEN1, exist in a looped conformation, effectively bringing together their promoter and terminator regions. We also show that PolII is located at both ends of FMP27 when this gene is transcribed from a GAL1 promoter under induced and noninduced conditions. Under these conditions, the C-terminal domain of the large subunit of PolII is phosphorylated at Ser5. Notably, inactivation of Kin28p causes a loss of both Ser5 phosphorylation and the loop conformation. These data suggest that gene loops are involved in the early stages of transcriptional activation. They also predict a previously unknown structural dimension to gene regulation, in which both ends of the transcription unit are defined before and during the transcription cycle.

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Figure 1: Density of active PolII across the FMP27 ORF.
Figure 2: PolII localizes in the promoter and terminator regions of GAL1::FMP27, causing looping of the intervening ORF.
Figure 3: GAL1::FMP27 and SEN1 exist in a loop conformation dependent on the expression state.
Figure 4: Model of the proposed GAL1::FMP27 gene loop.
Figure 5: Phosphorylation at Ser5 of PolII CTD is required for gene loop conformation.

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Acknowledgements

We thank K. Struhl for the FMP27 gene constructs, G. Faye for the GF 4044 kin28ts-4 strain and A. Binnie for advice on the 3C technique. This work was supported by a Programme Grant from the Wellcome Trust (to N.J.P.) and a Project Grant from the Biological and Biotechnology Science Research Council (to J.M.). J.C. was supported by a Nuffield Foundation Summer Studentship. A.M. is supported by the Human Frontier Science Program.

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Author notes

  1. Justin M O'Sullivan, Sue Mei Tan-Wong and Antonin Morillon: These authors contributed equally to this work.

Authors and Affiliations

  1. Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, UK

    Justin M O'Sullivan, Sue Mei Tan-Wong, Barbara Lee, Joel Coles & Nick J Proudfoot

  2. Department of Biochemistry, University of Oxford, South Parks Road, Oxford, UK

    Antonin Morillon & Jane Mellor

Authors
  1. Justin M O'Sullivan
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  2. Sue Mei Tan-Wong
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Correspondence to Nick J Proudfoot.

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Supplementary information

Supplementary Table 1

Positions of antisense RNA probes used in TRO analysis. (PDF 191 kb)

Supplementary Table 2

Positions of ChIP PCR primers on the GAL1:FMP27 gene. (PDF 47 kb)

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O'Sullivan, J., Tan-Wong, S., Morillon, A. et al. Gene loops juxtapose promoters and terminators in yeast. Nat Genet 36, 1014–1018 (2004). https://doi.org/10.1038/ng1411

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