Promoter and enhancer RNAs regulate chromatin reorganization and activation of miR-10b/HOXD locus and neoplastic transformation in glioma [ChIP-seq]

ABSTRACT: Using a combination of chromatin capture techniques, ChIP-Seq, single-molecule in situ RNA analysis, and computational analysis of large-scale TCGA datasets, we identified an epigenetic mechanism underlying common activation of HOXD/miR-10b locus in otherwise highly heterogenous glioma brain tumors. We demonstrate for the first time that two remote lncRNAs, one associated with a genomic promoter and another with a newly identified enhancer, cooperatively shape the 3D chromatin structure and looping, leading to the activation of a large gene cluster (12 genes, 110 KB) that includes the regulatory miRNA essential for glioma survival. This work describes a new mechanism contributing to neoplastic transformation in gliomagenesis, and identifies new avenues for therapeutic interventions based on the promoter and enhancer associated regulatory transcripts.

ORGANISM(S): Homo sapiens

PROVIDER: GSE161257 | GEO | 2021/11/11

REPOSITORIES: GEO