{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nHistone H2BC26 plays a central role in remodeling chromatin during the cellular response to DNA double‐strand breaks. Upon DNA damage, H2B is monoubiquitylated in an ATM‐dependent manner by the RNF20-RNF40 E3 ubiquitin ligase complex, a modification that facilitates chromatin relaxation and allows rapid recruitment of both nonhomologous end-joining and homologous recombination repair factors. This dynamic posttranslational modification is therefore essential for ensuring efficient and timely DNA repair."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n \nHistone H2BC26 is also implicated in modulating viral processes. In Epstein–Barr virus-infected cells, binding of the EBNA1 protein to viral oriP elements is stimulated by the cellular deubiquitylating enzyme USP7, whose activity, enhanced by its association with GMP synthetase (GMPS), includes the removal of monoubiquitin from H2B. This deubiquitylation event at viral genomes contributes to effective transcriptional activation from the oriP locus, highlighting a role for H2B modification in regulating viral latency and persistence."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n \nBeyond its nuclear functions, H2BC26 is displayed on the cell surface where it serves as a regulated plasminogen receptor. Elevated expression of H2B on activated monocytoid cells and neutrophils significantly enhances plasminogen binding, thereby modulating pericellular proteolysis and cell migration. This receptor function illustrates an unexpected extracellular role for a canonical histone in controlling cell behavior."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n \nMoreover, extrachromosomal H2BC26 has been shown to participate in innate immune responses against DNA viruses. It functions as an adaptor that, through interaction with the newly identified CIAO protein and IPS-1, facilitates type I interferon production specifically in response to double-stranded DNA. This mechanism underlines a critical contribution of H2B to antiviral defenses independent of its traditional chromatin-associated roles."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n \nFinally, the nuclear localization and staining of H2BC26 have been investigated in the context of sperm chromatin integrity, where its presence correlates with DNA damage. This finding suggests that H2B not only serves fundamental functions in the regulation of genomic processes but may also act as a biomarker for assessing sperm nuclear quality."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Lilach Moyal, Yaniv Lerenthal, Mali Gana-Weisz, et al. 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