Histone H4 lysine 20 monomethylation is not a mark of transcriptional silencers

Transcriptional silencers are cis-regulatory elements that downregulate the expression of target genes. Although thousands of silencers have been identified experimentally, a predictive chromatin signature of silencers has not been found. H4K20me1 previously was reported to be highly enriched among human silencers, but our reanalysis of the data using an appropriate background revealed that the enrichment is only marginal. We generated H4K20me1 ChIP-seq profiles in Drosophila S2 cells, which similarly showed that H4K20me1 does not mark Drosophila silencers and instead is associated with active transcription. Silencers remain a poorly annotated, difficult to predict class of cis-regulatory elements whose specific chromatin features remain to be identified.