Impaired histone inheritance promotes tumor progression
Creators
- 1. CAS Key Laboratory of Quantitative Engineering Biology, Guangdong Provincial Key Laboratory of Synthetic Genomics and Shenzhen Key Laboratory of Synthetic Genomics, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China
- 2. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
- 3. Hormel Institute, University of Minnesota, Austin, MN 55912 USA
- 4. Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, 55905 USA
- 5. Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, International Cancer Center, Marshall Laboratory of Biomedical Engineering, Shenzhen University Health Science Center, Shenzhen 518060, China
- 6. Department of Anatomy and Histology, Shenzhen University Health Science Center, Shenzhen 518060, China
- 7. Department of Biomedical Sciences, City University of Hong Kong, Hong Kong Special Administration Region, China
- 8. School of Pharmaceutical Science and Technology, Tianjin University and Health-Biotech United Group Joint Laboratory of Innovative Drug Development and Translational Medicine, Tianjin University, Tianjin 300072, China
Description
In this study, we constructed a model of impaired histone inheritance by introducing MCM2-2A mutation (defective in parental histone binding) in MCF-7 breast cancer cells. The resulting impaired histone inheritance reprogrammed the histone modification landscapes of progeny cells, especially the repressive histone mark H3K27me3. Lower H3K27me3 levels derepressed the expression of genes associated with development, cell proliferation, and epithelial to mesenchymal transition. Signal quantification was implemented mainly using custom Perl (v.5.26.2) scripts. These scripts calculated normalized densities of H3K36me3 for peak regions (± 10 kb from peak center) in which H3K27me3 was upregulated, stable, or downregulated in MCM2-2A mutant vs. WT cells. The scripts also calculated normalized densities of H3K36me3 for gene body regions (from TSS to TES) associated with promoters at which H3K4me3 was upregulated, stable, or downregulated in MCM2-2A mutant vs. WT cells, with a scan bin size of 100 bp. FPKM for defined regions, such as promoters and enhancers, were calculated with custom Perl scripts. Topologically associated domain analysis of MCF-7 and T47D H3K27me3 was implemented using custom python scripts.
Files
README.md
Files
(24.9 MB)
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