TRF2 and TRF1 are a key component in shelterin complex that associates with telomeric DNA and protects chromosome ends. BRM is a core ATPase subunit of SWI/SNF chromatin remodeling complex. Whether and how BRM-SWI/SNF complex is engaged in chromatin end protection by telomeres is unknown. Here, we report that depletion of BRM does not affect heterochromatin state of telomeres, but results in telomere dysfunctional phenomena including telomere uncapping and replication defect. Mechanistically, expression of TRF2 and TRF1 is jointly regulated by BRM-SWI/SNF complex, which is localized to promoter region of both genes and facilitates their transcription. BRM-deficient cells bear increased TRF2-free or TRF1-free telomeres due to insufficient expression. Importantly, BRM depletion-induced telomere uncapping or replication defect can be rescued by compensatory expression of exogenous TRF2 or TRF1, respectively. Together, these results identify a new function of BRM-SWI/SNF complex in enabling functional telomeres for maintaining genome stability.

TRF2和TRF1是掩护蛋白复合物中的关键成分，该复合物与端粒DNA缔合并保护染色体末端。BRM是SWI / SNF染色质重塑复合体的核心ATPase亚基。BRM-SWI / SNF复合物是否以及如何通过端粒参与染色质末端保护尚不清楚。在这里，我们报告说，BRM的消耗不会影响端粒的异染色质状态，但会导致端粒功能异常现象，包括端粒解封和复制缺陷。从机制上讲，TRF2和TRF1的表达受BRM-SWI / SNF复合体共同调节，该复合体位于两个基因的启动子区域，并促进其转录。由于表达不足，缺乏BRM的细胞带有增加的无TRF2或无TRF1的端粒。重要的，可以分别通过外源性TRF2或TRF1的补偿性表达来挽救BRM耗竭诱导的端粒解键或复制缺陷。总之，这些结果确定了BRM-SWI / SNF复合体在启用功能性端粒以维持基因组稳定性方面的新功能。