Histone modification profiling in breast cancer cell lines highlights commonalities and differences among subtypes

Abstract

BackgroundEpigenetic regulators are frequently mutated or aberrantly expressed in a variety of cancers, leading to altered transcription states that result in changes in cell identity, behavior, and response to therapy.ResultsTo define alterations in epigenetic landscapes in breast cancers, we profiled the distributions of 8 key histone modifications by ChIP-Seq, as well as primary (GRO-seq) and steady state (RNA-Seq) transcriptomes, across 13 distinct cell lines that represent 5 molecular subtypes of breast cancer and immortalized human mammary epithelial cells.DiscussionUsing combinatorial patterns of distinct histone modification signals, we defined subtype-specific chromatin signatures to nominate potential biomarkers. This approach identified AFAP1-AS1 as a triple negative breast cancer-specific gene associated with cell proliferation and epithelial-mesenchymal-transition. In addition, our chromatin mapping data in basal TNBC cell lines are consistent with gene expression patterns in TCGA that indicate decreased activity of the androgen receptor pathway but increased activity of the vitamin D biosynthesis pathway.ConclusionsTogether, these datasets provide a comprehensive resource for histone modification profiles that define epigenetic landscapes and reveal key chromatin signatures in breast cancer cell line subtypes with potential to identify novel and actionable targets for treatment.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-4533-0) contains supplementary material, which is available to authorized users.

A Tumor-Specific Super-Enhancer Drives Immune Evasion by Guiding Synchronous Expression of PD-L1 and PD-L2

“…We analyzed the H3K27Ac chromatin immunoprecipitation sequencing (ChIP-seq) data in a panel of 13 cell lines including two immortalized breast cell lines, two luminal A breast cancer cell lines, two luminal B breast cancer cell lines, three HER2-positive breast cancer cell lines, and four triple-negative breast cancer cell lines ( Figure 7A). A summary of the characteristics of these 13 breast cancer cell lines was described previously (Franco et al, 2018;Xi et al, 2018). Profiling histone modification and RNA transcription revealed that distinct breast cancer subtypes show unique epigenomes and active enhancers Xi et al, 2018).…”

Crosstalk between microRNA expression and DNA methylation drive the hormone-dependent phenotype of breast cancer

“…With GSEA using Enrichr [22], we found these genes enriched in signaling and cancer-associated pathways such as the Ras and PI3K-Akt signaling pathways (Additional file 4h). According to the ChromHMM genome segmentation of breast cancer cell lines [29], cluster 1 CpGs were enriched at enhancers, especially of ER positive/luminal cell lines ( Figure 2a and Additional file 4i). ATAC-seq data from TCGA confirmed that the regions surrounding these CpGs were more accessible (open) in ER positive than in ER negative tumors (Wilcoxon p-value = 6.38e-5; Figure 2b).…”

“…For functional annotation of the CpGs, we utilized the ChromHMM segmentation from Xi et al [29] obtained from cell lines representing different breast cancer molecular subtypes [29]…”

“…Functional annotation of the CpG clusters. a) Genomic location enrichment of mimQTL CpGs in cluster 1 according to ChromHMM data from cell lines representing different breast cancer subtypes[29]. Active Genic Enhancer=Act_Gen_Enh…”

Fluctuations of Histone Chemical Modifications in Breast, Prostate, and Colorectal Cancer: An Implication of Phytochemicals as Defenders of Chromatin Equilibrium

“…Disequilibrium of catalytic activity of enzymes and thus alterations of PHMs patterns are directly connected to BC, PC, and CRC initiation and promotion [34,[101][102][103]. Therefore, individual patterns of histone modifications might be implicated as markers of response to treatment and their specific motifs can correlate with cancer recurrence and overall survival of patients [104,105].…”