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Nat Genet. 2014 Sep;46(9):973-981. doi: 10.1038/ng.3058. Epub 2014 Aug 10.

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

Author information

IMBA, Institute of Molecular Biotechnology GmBH, Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, 79108 Freiburg, Germany.
CeMM, Research Center for Molecular Medicine, Lazarettgasse 14, 1090 Vienna, Austria.
IMP, Institute of Molecular Pathology, Dr. Bohr-Gasse 7, 1030 Vienna, Austria.
The Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, United Kingdom.
Department of Genetics, Cell Biology and Development, University of Minnesota. Minneapolis, Minnesota, USA.
Contributed equally


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.

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