PLX036490

GSE108693: Luminal lncRNAs Regulation by ER-controlled Enhancers in a Ligand-independent Manner in Breast Cancer Cells

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

Estrogen receptor- (ER) is a ligand-inducible protein which mediates estrogenic hormones signaling and defines the luminal breast cancer phenotype. Recently, we demonstrated that ER binds chromatin in absence of ligand (apoER) regulating transcription of protein-coding genes and several lncRNAs. Noteworthy, apoER-regulated lncRNAs marginally overlap estrogen-induced transcripts representing a signature of luminal breast cancer genes. DSCAM-AS1 is a paradigmatic example of apoER activity since its expression is largely unaffected by estrogenic treatment despite an E2-induced increment of ER binding on its promoter. Analysing H3K27ac ChIP-Seq performed in hormone-deprived MCF-7, we identified a set of Super Enhancers (SEs) occupied by apoER including one mapped in proximity of DSCAM-AS1. Using ChIP-qPCR, we validated ChIP-Seq signal of apoER, p300 and CTCF at both DSCAM-AS1 TSS and at its associated SE. Furthermore, analysing MCF-7 ChIA-PET data and performing a 3C experiment, we confirmed a long range chromatin interaction between the SE and the DSCAM-AS1 TSS. Interestingly, CTCF binding downstream to DSCAM-AS1 shows an enrichment in hormone-depleted medium as compared to other experimental conditions, indicating that CTCF demarcates enhancer actions at DSCAM-AS1 locus. The analysis of this lncRNA provides a paradigm of transcriptional regulation of a luminal specific apoER regulated lncRNA. SOURCE: Giulio Ferrero University of Turin