An interdependent network of functional enhancers regulates transcription and EZH2 loading at the INK4a/ARF locus.

ABSTRACT: The INK4a/ARF locus encodes important cell-cycle regulators p14^ARF, p15^INK4b, and p16^INK4a. The neighboring gene desert to this locus is the most reproducible GWAS hotspot that harbors one of the densest enhancer clusters in the genome. However, how multiple enhancers that overlap with GWAS variants regulate the INK4a/ARF locus is unknown, which is an important step in linking genetic variation with associated diseases. Here, we show that INK4a/ARF promoters interact with a subset of enhancers in the cluster, independent of their H3K27ac and eRNA levels. Interacting enhancers transcriptionally control each other and INK4a/ARF promoters over long distances as an interdependent single unit. The deletion of even a single interacting enhancer results in an unex

SUBMITTER: Farooq U 

PROVIDER: S-EPMC7611173 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature