CRISPR screens identify gene targets at breast cancer risk loci [ATAC-seq]

Genome-wide association studies (GWAS) have identified >200 loci associated with breast cancer (BC) risk. The majority of candidate causal variants (CCVs) are in non-coding regions and likely modulate cancer risk by regulating gene expression. However, pinpointing the exact target of the association, and identifying the phenotype it mediates, is a major challenge in the interpretation and translation of GWAS. Overall design: Transcriptome, open chromatin, and chromatin interaction profiling using RNA-seq, ATAC-seq and H3K27ac-mediated HiChIP of six immortalized mammary epithelial cell lines representing breast cells with either a luminal progenitor signature (K5+/K19+, K5+/K19-), a mesenchymal signature (B80-T17, mesHMLE) or a more epithelial like signature (B80-T5, HMLE)

全基因组关联研究（Genome-wide association studies, GWAS）已鉴定出200余个与乳腺癌（breast cancer, BC）风险相关的基因座。绝大多数候选致病变异（candidate causal variants, CCVs）位于非编码区域，且极有可能通过调控基因表达来调节癌症风险。然而，精准定位该关联的具体作用靶点，并明确其介导的表型，仍是全基因组关联研究解读与转化过程中的一大核心挑战。实验整体设计：本研究采用RNA测序（RNA-seq）、转座酶可及性测序（ATAC-seq）以及H3K27乙酰化介导的HiChIP（H3K27ac-mediated HiChIP）技术，对6株永生化乳腺上皮细胞系开展转录组、开放染色质与染色质互作组谱学分析。所选用的细胞系分别代表具有不同分子特征的乳腺细胞：腔面祖细胞型（K5+/K19+、K5+/K19-）、间质型（B80-T17、mesHMLE）以及上皮样表型（B80-T5、HMLE）