Integrated ChIP-seq and Transcriptomic Profiling of Histone Modifications Across Breast Cancer Progression in MCF10A-Derived Cell Lines [ChIP-Seq]
Cancer arises from complex epigenetic mechanisms that drive tumorigenesis. Gene regulatory elements play a pivotal role in reprogramming gene expression patterns, facilitating tumor initiation, progression, and metastasis. However, a comprehensive characterization of epigenetic alterations across cancer development remains incomplete, particularly for the spectrum of post-translational histone modifications in the evolution of breast tumors. In this study, we explored the dynamic landscape of epigenetic changes using a breast cancer progression model based on the MCF10A cell line. We integrated ChIP-seq and transcriptomic profiling to investigate the epigenetic heterogeneity across four MCF10A-derived cancer cell lines: normal (MCF10A), HRAS G12V transformed, ductal carcinoma in situ (DCIS), and metastatic (CA1a). Our analysis revealed significant changes in chromatin patterns at regulatory elements, including stage-specific variability in H3K27me3 and H3K9me3-marked heterochromatin domains.  These profiles underly the epigenomic changes in each of these cell states to provide insights into human breast cancer progression. Overall design: This study includes an analysis of ChIP-seq data from four MCF10A-derived cell lines representing different stages of breast cancer progression: normal (MCF10A), HRAS G12V transformed, ductal carcinoma in situ (DCIS), and metastatic (CA1a). We investigated the epigenetic changes through ChIP-seq profiling of histone modifications (H3K27me3, H3K9me3, H3K4me1, H3K27ac, H4K5ac, H4K8ac). Biological replicates were included to ensure robustness and reproducibility of the data.