Effects of dominant-negative Smarca4 mutations on the DNA accessibility landscape [ATAC-seq]

We generated a library of Smarca4 variants with mutations in conserved regions of the N-terminal ATPase domain based on mutants observed in primary tumors and cancer cell lines. Heterozygous expression of Smarca4 ATPase mutants led to decreased accessibility at active enhancers in mouse embryonic stem cells. Examination of genomic accessibility using ATAC-seq in mouse embryonic stem (ES) cells expressing heterozygous mutations of the BAF subunit Smarca4. Cells express wild-type Smarca4-GFP and either wild-type or mutants of Smarca4-V5. Filenames and descriptions of Smarca4 in this dataset refer to the status of the Smarca4-V5 fusion in these cells.

本研究基于原发肿瘤及癌细胞系中发现的突变体，构建了在N端ATP酶（ATPase）结构域保守区域携带突变的Smarca4变异体文库。Smarca4 ATP酶突变体的杂合表达会导致小鼠胚胎干细胞中活性增强子区域的染色质可及性降低。本研究通过ATAC-seq（转座酶可及性测序）技术，对表达BAF亚基Smarca4杂合突变的小鼠胚胎干细胞（ES细胞）的基因组可及性进行了检测。这些细胞同时表达野生型Smarca4-GFP，以及野生型或突变型Smarca4-V5。本数据集内Smarca4的文件名及相关描述，均指代这些细胞中Smarca4-V5融合蛋白的状态。