Fig. 1

Non-classical functions of HMRs and ncHMR detector framework. a Schematic showing classical and non-classical functions of HMRs. Classical functions of HMRs include recognizing (CBX7 recognizes H3K27me3), adding (RNF2 catalyzes H2Aub1), or removing (KDM2B demethylates H3K36me2) histone modification substrates/products. In contrast, non-classical functions of HMRs are independent of its classical histone modification substrates/products and some involve in cooperation with other cofactors (EZH2 interacts with AR to activate gene transcription independently of H3K27me3). b Graph showing the classical and non-classical binding sites of EZH2 in abl cell line. The red line indicates the distribution of H3K27me3 signals at EZH2 ChIP-seq peaks. The light blue and green dashed lines indicate two fitted normal distributions for H3K27me3 signals which represent non-classical sites without H3K27me3 and classical sites with H3K27me3, respectively. The pie chart shows the number of two kinds of binding sites. c Heatmap showing EZH2, H3K27me3, and E2F1 enrichment around EZH2 ChIP-seq peak centers in abl cell line. Rows represent EZH2 binding sites and are ranked by normalized H3K27me3 signals. The colors indicate the normalized ChIP-seq enrichment level and the values are scaled by row. d A schematic view of the workflow of the ncHMR detector framework (see the “Methods” section for details). All ChIP-seq data used in the analysis were annotated in Additional file 1: Fig. S1a