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5-formylcytosine and 5-carboxylcytosine reduce the rate and substrate specificity of RNA polymerase II transcription

Nature Structural & Molecular Biology volume 19, pages 831–833 (2012)Cite this article

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Abstract

Although the roles of 5-methylcytosine and 5-hydroxymethylcytosine in epigenetic regulation of gene expression are well established, the functional effects of 5-formylcytosine and 5-carboxylcytosine on the process of transcription are not clear. Here we report a systematic study of the effects of five different forms of cytosine in DNA on mammalian and yeast RNA polymerase II transcription, providing new insights into potential functional interplay between cytosine methylation status and transcription.

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Figure 1: Cytosine methylation status affects mammalian and yeast RNA polymerase II transcription.
Figure 2: Pol II polymerization rate and specificity of GTP incorporation for C, 5hmC, 5fC and 5caC templates.
Figure 3: 5fC reduces Pol II substrate discrimination of GTP over ATP.

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Acknowledgements

D.W. acknowledges support from the US National Institutes of Health (GM085136), start-up funds from the Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California, San Diego, and the Kimmel Scholar Award from the Sidney Kimmel Foundation for Cancer Research. C.H. acknowledges the National Institutes of Health for support (GM071440). We thank J. Conaway and R. Conaway (Stowers Institute for Medical Research) for the generous gift of purified mammalian Pol II. We also thank E.P. Geiduschek, J.R. Halpert, X-D. Fu, B. Ren, Y. Zhang and K. Zhang for their insightful comments and critical reading of the manuscript.

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Authors and Affiliations

  1. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA.,

    Matthew W Kellinger, Jenny Chong & Dong Wang

  2. Department of Chemistry and Institute for Biophysical Dynamics, University of Chicago, Chicago, Illinois, USA

    Chun-Xiao Song, Xing-Yu Lu & Chuan He

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  1. Matthew W Kellinger
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Contributions

D.W. conceived the original idea. M.W.K., C.H. and D.W. designed the experiments. C.S. and X.L. carried out synthesis of DNA templates. J.C. and D.W. purified Pol II. M.W.K. and D.W. performed transcription assays. M.W.K. and D.W. carried out data analysis. M.W.K., J.C., C.H. and D.W. wrote the paper.

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Correspondence to Dong Wang.

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The authors declare no competing financial interests.

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Supplementary Figures 1–5, Supplementary Tables 1–3 and Supplementary Note (PDF 3097 kb)

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Kellinger, M., Song, CX., Chong, J. et al. 5-formylcytosine and 5-carboxylcytosine reduce the rate and substrate specificity of RNA polymerase II transcription. Nat Struct Mol Biol 19, 831–833 (2012). https://doi.org/10.1038/nsmb.2346

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