BRG1 interaction with chromatin and BRG1-dependent transcriptome in non-resistant and paclitaxel-resistant MDA-MB-231

The BRG1 redistribution, de novo recruitment and extrusion from chromatin in response to multiple doses of paclitaxel was studied by ChIP-Seq. The applied taxen was added to cells at the concentration of 0.05 uM for 48 h every 3 weeks for a total number of 6 cycles. The treatment scheme was chosen to fit the current therapeutic approaches, and drug concentration to fit the minimal paclitaxel concentration in the blood of patients. The impact of BRG1 on cell transcriptome was tested in BRG1 transiently silenced cells (72 h after transfection with siRNA).

本研究采用染色质免疫共沉淀测序（ChIP-Seq）技术，对多次紫杉醇暴露后BRG1的染色质重新分布、从头招募以及从染色质中解离的过程进行了探究。实验中所用的紫杉醇以0.05 μM的浓度处理细胞，每3周给药一次，每次持续48小时，共计完成6个循环周期。该给药方案贴合当前临床治疗策略，药物浓度匹配患者血液中紫杉醇的最低有效血药浓度。本研究还通过小干扰RNA（siRNA）转染细胞72小时后构建的BRG1瞬时沉默细胞模型，检测了BRG1对细胞转录组的影响。