GSE201262
Impaired histone inheritance promotes tumor progression
In this study, we constructed a tumor model of impaired inheritance of parental histones by introducing an MCM2 histone-binding domain (HBD) mutation in the breast cancer cell lines MCF-7. In this model, impaired histone inheritance resulted in dramatic epigenetic reprogramming, especially the pattern of the repressive histone mark H3K27me3, and promoted tumor growth and metastasis in vivo. Overall design: We used breast cancer MCF-7 cell line (Wild type and MCM2-2A mutant cells) in this study. ATAC-seq method was used to evaluate the chromatin accessibility and CUT&Tag-seq and ChIP-seq were adopted to study the chromatin-binding affinity of histones, histone marks and their associated complex members. In both WT and MCM2-2A MCF-7 cells, we employed ATAC-seq, CUT&Tag-seq of H3.3, H3K27me3, H3K27ac, H3K9me3, H3K4me3, H3K4me1, H3K36me3, SUZ12, H2AK119ub and RING1B, as well as ChIP-seq of H3K36me2 and EZH2. H3K27me3 CUT&Tag experiments above were also implemented in POLE3 KO MCF7 cells. In addition, CUT&Tag for H3K27me3, H3K4me3 and H3.3 were performed in WT and MCM2-2A mutant HEK293T cells, as well as in WT and MCM2-90A mutant T47D cells.  Bulk RNA-seq and scRNA-seq in vitro and in vivo were also implememted.