BAP18 facilitates CTCF-mediated chromatin accessible to regulate enhancer activity in breast cancer

The estrogen receptor alpha (ER alpha) signaling pathway is a crucial target for ER alpha-positive breast cancer therapeutic strategies. Co-regulators and other transcription factors cooperate for effective ER alpha-related enhancer activation. Recent studies demonstrate that the transcription factor CTCF is essential to participate in ER alpha/E2-induced enhancer transactivation. However, the mechanism of how CTCF is achieved remains unknown. Here, we provided evidence that BAP18 is required for CTCF recruitment on ER alpha-enriched enhancers, facilitating CTCF-mediated chromatin accessibility to promote enhancer RNAs transcription. Consistently, GRO-seq demonstrates that the enhancer activity is positively correlated with BAP18 enrichment. Furthermore, BAP18 interacts with SMARCA1/BPTF to accelerate the recruitment of CTCF to ER alpha-related enhancers. Interestingly, BAP18 is involved in chromatin accessibility within enhancer regions, thereby increasing enhancer transactivation and enhancer-promoter looping. BAP18 depletion increases the sensitivity of anti-estrogen and anti-enhancer treatment in MCF7 cells. Collectively, our study indicates that BAP18 coordinates with CTCF to enlarge the transactivation of ER alpha-related enhancers, providing a better understanding of BAP18/CTCF coupling chromatin remodeling and E-P looping in the regulation of enhancer transcription.

Automated summary

A study found that BAP18 cooperates with CTCF to participate in the transcriptional activation of ER alpha-related enhancers, increasing their accessibility and promoting enhancer RNA transcription. BAP18 also interacts with SMARCA1/BPTF to accelerate the recruitment of CTCF to ER alpha-related enhancers. Depletion of BAP18 increases sensitivity to anti-estrogen and anti-enhancer treatment in MCF7 cells.