Fig. 5: Distal regulatory element in the LINC01488 locus.
From: Subtype and cell type specific expression of lncRNAs provide insight into breast cancer
a Enrichment of CpGs with DNA methylation significantly inversely correlated with lncRNA expression across ChromHMM genome segmentation from breast cancer cell lines. Enrichment is calculated by comparing the genomic location of the CpG inversely correlated to all the CpGs on the 450k Illumina array as background. Active Enhancer = EhAct, Ehnancer Genic = EhGen, Transcription flanking = TxFlk. Average normalized counts for ATAC-seq peaks mapped to CpG location for which DNA methylation is significantly inversely correlated with lncRNAs with higher expression in ER positive cases (b) and higher expression in ER negative cases (c). ATAC-seq data from ER + (blue dots) (n = 58) and ER- (red dots) (n = 12) breast tumor samples from the TCGA-BRCA cohort. Wilcoxon test p-values are denoted. The line within each box represents the median. Upper and lower edges of each box represent 75th and 25th percentile, respectively. The whiskers represent the lowest datum still within [1.5 × (75th − 25th percentile)] of the lower quartile, and the highest datum still within [1.5 × (75th − 25th percentile)] of the upper quartile. d Swarm plot showing enrichment of TF binding sites (–(log10(p-value) using Fisher’s exact tests) on the y-axis for CpGs with DNA methylation inversely correlated with lncRNA expression. Names of the top 10 enriched TF binding sites data sets are annotated by colours. e Graphical illustration of the LINC01488 locus annotated for different epigenomic tracks. CpGs measured by the 450 k Illumina array are shown together with the significant negative correlations between levels of DNA methylation and LINC01488 expression in the OSLO2 and TCGA cohorts (blue arcs, negative expression-methylation correlation). ChromHMM Enhancer regions (active and genic) in the Mcf7 cell line (green) with ChiA-PET polII loop connecting the TSS of LINC01488 to the CpG in the enhancer region (pink arcs). TF binding of ESR1 (dark blue), FOXA1 (blue), and GATA3 (light blue) from ChIP-seq experiments (ReMap). f, g Correlation plot of levels of LINC01488 expression (x-axis) and levels of DNA methylation of the CpG (y-axis) in long-range interaction in e. Rho and p-value from Spearman correlation is indicated. f OSLO2 (ER positive, n = 214, ER negative, n = 52), g TCGA (ER positive, n = 807, ER negative, n = 237. h Graphical illustration of the LINC01488 locus annotated with ChromHMM Enhancer regions (active and genic) in the Mcf7 cell line (green) and ChiA-PET polII loop connecting LINC01488 to CCND1 (pink arcs). i Correlation plot of log2(TPM + 1) LINC01488 expression (x-axis) and log2(TPM + 1) CCND1 expression (y-axis) in ER positive (n = 2409) and ER negative (n = 504) patients in the SCAN-B cohort. Rho and p-value from Spearman correlation are indicated.
