A strand-specific switch in noncoding transcription switches the function of a Polycomb/Trithorax response element

Veronika A. Herzog, Adelheid Lempradl, Johanna Trupke, Helena Okulski, Christina Altmutter, Frank Ruge, Bernd Boidol, Stefan Kubicek, Gerald Schmauss, Karin Aumayr, Marius Ruf, Andrew Pospisilik, Andrew Dimond, Hasene Basak Senergin, Marcus L. Vargas, Jeffrey A. Simon, Leonie Ringrose

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Abstract

Polycomb/Trithorax response elements (PRE/TREs) can switch their function reversibly between silencing and activation by mechanisms that are poorly understood. Here we show that a switch in forward and reverse noncoding transcription from the Drosophila melanogaster vestigial (vg) PRE/TRE switches the status of the element between silencing (induced by the forward strand) and activation (induced by the reverse strand). In vitro, both noncoding RNAs inhibit PRC2 histone methyltransferase activity, but, in vivo, only the reverse strand binds PRC2. Overexpression of the reverse strand evicts PRC2 from chromatin and inhibits its enzymatic activity. We propose that the interaction of RNAs with PRC2 is differentially regulated in vivo, allowing regulated inhibition of local PRC2 activity. Genome-wide analysis shows that strand switching of noncoding RNAs occurs at several hundred Polycomb-binding sites in fly and vertebrate genomes. This work identifies a previously unreported and potentially widespread class of PRE/TREs that switch function by switching the direction of noncoding RNA transcription.

Original languageEnglish (US)
Pages (from-to)973-981
Number of pages9
JournalNature Genetics
Volume46
Issue number9
DOIs
StatePublished - Jan 1 2014

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Herzog, V. A., Lempradl, A., Trupke, J., Okulski, H., Altmutter, C., Ruge, F., Boidol, B., Kubicek, S., Schmauss, G., Aumayr, K., Ruf, M., Pospisilik, A., Dimond, A., Senergin, H. B., Vargas, M. L., Simon, J. A., & Ringrose, L. (2014). A strand-specific switch in noncoding transcription switches the function of a Polycomb/Trithorax response element. Nature Genetics, 46(9), 973-981. https://doi.org/10.1038/ng.3058