Fig. 3

Histone variants in the regulation of cell cycle in breast cancer. a Enrichment of H2A.Z in the c-MYCpromoter induces c-Myc expression. c-MYC in turn inhibits p21 [cell cycle inhibitor] thereby leading the cells into cell cycle. H2A.Z also causes p21/p51 transcriptional repression by binding to the later’s promoter region. H2A.Z knockdown induce EMT in MCF-10A. b (i) MacroH2A.2 recruits EZH2 which causes H3K27me3 repressive mark in the promoter region of LOX gene. LOX causes change in the αvβ₃ integrin which causes phosphorylation of c-SRC causing cytoskeleton and ECM remodeling and finally leading to breast cancer bone metastasis. b (ii) SCF SKP2 causes ubiquitination and degradation of MacroH2A1, leading to CDK8 upregulation followed by Cyclin A/CDK2 recruitment, which causes cell proliferation. Besides, SCF SKP2, CDK8 and Cyclin A/CDK2 also ubiquitinates cell cycle inhibitor p27