Luminal lncRNAs Regulation by ER?-Controlled Enhancers in a Ligand-Independent Manner in Breast Cancer Cells.

ABSTRACT: Estrogen receptor-? (ER?) is a ligand-inducible protein which mediates estrogenic hormones signaling and defines the luminal BC phenotype. Recently, we demonstrated that even in absence of ligands ER? (apoER?) binds chromatin sites where it regulates transcription of several protein-coding and lncRNA genes. Noteworthy, apoER?-regulated lncRNAs marginally overlap estrogen-induced transcripts, thus representing a new signature of luminal BC genes. By the analysis of H3K27ac enrichment in hormone-deprived MCF-7 cells, we defined a set of Super Enhancers (SEs) occupied by apoER?, including one mapped in proximity of the DSCAM-AS1 lncRNA gene. This represents a paradigm of apoER? activity since its expression is largely unaffected by estrogenic treatment, despite the fact that E2 increases ER? binding on DSCAM-AS1 promoter. We validated the enrichment of apoER?, p300, GATA3, FoxM1 and CTCF at both DSCAM-AS1 TSS and at its associated SE by ChIP-qPCR. Furthermore, by analyzing MCF-7 ChIA-PET data and by 3C assays, we confirmed long range chromatin interaction between the SE and the DSCAM-AS1 TSS. Interestingly, CTCF and p300 binding showed an enrichment in hormone-depleted medium and in the presence of ER?, elucidating the dynamics of the estrogen-independent regulation of DSCAM-AS1 expression. The analysis of this lncRNA provides a paradigm of transcriptional regulation of a luminal specific apoER? regulated lncRNA.

SUBMITTER: Miano V 

PROVIDER: S-EPMC5855815 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature