UC San Diego

Increasing evidence reveals the rather massive transcription of non-coding RNA (ncRNA) transcripts in mammalian cells, including bidirectional transcripts at enhancer sites, referred to as eRNAs; however, it has remained unclear whether these eRNAs are functional, or merely a reflection of altered enhancer chromatin. Here, we report that estrogen receptor [alpha] (ER[alpha]) causes an upregulation of eRNAs on ER[alpha]-bound activated enhancers that is required both for specific enhancer:promoter looping, and for activation of E₂- regulated coding target genes. Estrogen regulated recruitment of the cohesin complex to enhancers, the ER[alpha] mediated relocation of induced target genes from the repressive environment of the polycomb body to the activating environment of the interchromatin granule, and the enhanced strength of specific enhancer:promoter looping, are all eRNA dependent events. Enhancer functions involve the ability of eRNAs to interact with WDR82 (a component of the COMPASS complex), as well as reading the H3K4me3 mark. Our data suggest that eRNAS are likely to exert important functions in many regulated programs of gene expression, ultimately based on their roles in altering long range chromatin interactions and the location of regulated transcription units between functionally-distinct subnuclear architectural structures