雌激素受体a (ERα) 信号通路是ERα阳性乳腺癌治疗策略的关键目标。共激活因子和其他转录因子合作，以有效激活ERα相关增强子。最近的研究表明，转录因子CTCF对于参与ERα / E2诱导的增强子转录活化是必不可少的。然而，CTCF如何实现的机制仍然未知。在这里，我们提供证据，表明BAP18是必需的，用于在ERα浓缩的增强子上招募CTCF，促进CTCF介导的染色质可及性，以促进增强子RNA转录。一致地，GRO-seq表明增强子活性与BAP18富集呈正相关。此外，BAP18与SMARCA1 / BPTF相互作用，以加速将CTCF招募到ERα相关增强子上。有趣的是，BAP18参与了增强子区域内染色质可及性，从而增加了增强子转录和增强子-启动子环路。BAP18消耗会增加MCF7细胞对抗雌激素和抗增强子治疗的敏感性。总的来说，我们的研究表明BAP18与CTCF协调作用，以扩大ERα相关增强子的转录活化，进一步提高了BAP18 / CTCF耦合染色质重塑和E-P环路在增强子转录调控中的理解。 ©2023。作者（s）在ADMC分化与细胞死亡协会的独家许可下。

The estrogen receptor alpha (ERα) signaling pathway is a crucial target for ERα-positive breast cancer therapeutic strategies. Co-regulators and other transcription factors cooperate for effective ERα-related enhancer activation. Recent studies demonstrate that the transcription factor CTCF is essential to participate in ERα/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 ERα-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 ERα-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 ERα-related enhancers, providing a better understanding of BAP18/CTCF coupling chromatin remodeling and E-P looping in the regulation of enhancer transcription.© 2023. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.