Journal
MOLECULAR CELL
Volume 38, Issue 5, Pages 675-688Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2010.03.019
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Funding
- MRC
- UCLH/UCL Comprehensive Biomedical Research Centre
- MAC Centre for Medical Molecular Virology
- NIH [HG002668, NS055923]
- Orion-Farmos Research Foundation
- Academy of Finland
- Medical Research Council [G0600081, G9721629, MC_U120061476, G0900950, G9721629B, G0900950B, MC_U120027516] Funding Source: researchfish
- MRC [MC_U120061476, G0600081, MC_U120027516, G9721629, G0900950] Funding Source: UKRI
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Polycomb proteins maintain cell identity by repressing the expression of developmental regulators specific for other cell types. Polycomb repressive complex-2 (PRC2) catalyzes trimethylation of histone H3 lysine-27 (H3K27me3). Although repressed, PRC2 targets are generally associated with the transcriptional initiation marker H3K4me3, but the significance of this remains unclear. Here, we identify a class of short RNAs, similar to 50-200 nucleotides in length, transcribed from the 5' end of polycomb target genes in primary T cells and embryonic stem cells. Short RNA transcription is associated with RNA polymerase II and H3K4me3, occurs in the absence of mRNA transcription, and is independent of polycomb activity. Short RNAs form stem-loop structures resembling PRC2 binding sites in Xist, interact with PRC2 through SUZ12, cause gene repression in cis, and are depleted from polycomb target genes activated during cell differentiation. We propose that short RNAs play a role in the association of PRC2 with its target genes.
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