{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n KDM5B (also known as JARID1B or PLU-1) is a histone H3 lysine 4 demethylase that removes active methyl marks from promoters, gene bodies, and enhancers to modulate gene expression programs in diverse biological contexts. In cancer, elevated KDM5B levels are observed in several malignancies, where it appears to contribute to tumor growth and cellular plasticity by maintaining a subpopulation of slow‐cycling, tumorigenic cells – for instance in melanoma – and by modulating transcriptional heterogeneity and endocrine resistance in breast cancer cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In parallel, mechanistic studies have demonstrated that KDM5B demethylates di‐, tri‐, and mono‐methylated H3K4, thereby repressing genes that control cell cycle progression and proliferation, a function supported by findings in prostate and bladder cancer cell models."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In luminal breast tumors, KDM5B plays a role in sustaining cell-specific transcriptional programs, while in triple-negative breast cancer models it acts to suppress cell migration and invasion through distinct chromatin-reading domains."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role in carcinogenesis, KDM5B is critical for proper epigenomic organization during development. In embryonic stem cells, it helps to focus H3K4 methylation at promoters and enhancers, ensuring accurate gene expression during self-renewal and differentiation; dysregulation of KDM5B activity leads to defects in cell fate decisions by allowing aberrant spreading of H3K4 methylation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "and impairs differentiation programs. Moreover, KDM5B has been implicated in the maintenance of genome stability through its role in the DNA damage response, where its demethylation of H3K4 near double-strand breaks facilitates the recruitment of essential repair factors, underscoring its function as a caretaker of chromatin integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Alexander Roesch, Mizuho Fukunaga-Kalabis, Elizabeth C Schmidt, et al. 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