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Figure 4 | BMC Genomics

Figure 4

From: Comparative DNA methylome analysis of endometrial carcinoma reveals complex and distinct deregulation of cancer promoters and enhancers

Figure 4

DNA methylation alterations are enriched in functional promoters and enhancers. (A) Four DNA methylation state patterns across embryonic stem cells (H1), normal endometrium (NE), and endometrial cancer (EC). Red block: methylated state; empty: unmethylated state. (B) Fractions of DMRs with different DNA methylation state patterns in EAC (left) and UPSC (right). DMRs with patterns MMU (yellow), UUM (green), and MUM (blue) were annotated by chromHMM for their potential regulatory functions (purple: promoter; orange: enhancer state; gray: other states). (C) Functional enrichment of DMRs in pattern MMU, UUM, and MUM by GREAT analysis (purple: DMRs annotated as promoters by chromHMM; orange: DMRs annotated as enhancers by chromHMM). X-axis denotes negative log10-transformed p-value. (D) Epigenome Browser views of representative DMRs with different methylation state patterns. MeDIP-seq signal tracks were displayed. Increased and decreased methylation levels were highlighted by pink and green shading, respectively. Left (pattern MMU): a DMR overlapped with transposable element MER52A was methylated in normal endometrium, H1 ESC, PBMC, and fetal brain, but unmethylated in breast myoepithelial cells. In EAC and UPSC, the element was hypomethylated, indicated by decreased MeDIP-seq signal. Middle (pattern UUM): a DMR overlapped with CGI of lncRNA LOC100130992 was unmethylated in normal endometrium, H1 ESC, and PBMC, but methylated in breast myoepithelial and fetal brain. The element was hypermethylated in EAC and UPSC. Right (pattern MUM): a DMR overlapped with CGI-shore of ADCY3 was methylated in all other tissues except in normal endometrium. In EAC and UPSC, this element was hypermethylated. (E) TIAM2 expression in normal controls and grade 3 pre-classified (microsatellite state, and subtype) endometrial cancer patients samples. Y-axis: calculated RPKM value based on mRNA-seq from TCGA. Asterisk indicates P <0.01, caret indicates P <0.05, Student’s t-Test. (F) The MER52A element enhanced luciferase reporter gene expression in HEK-293T cells. Blue: mini promoter; orange: MER52A + mini promoter.

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