{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n HMGN1 is a multifunctional nucleosome‐binding protein that plays a central role in modulating chromatin structure and function. By binding to nucleosomes, HMGN1 alters higher‐order chromatin organization and facilitates changes in key histone posttranslational modifications—such as reducing excessive H3S10 phosphorylation and enhancing H3K14 acetylation—thereby fine‐tuning transcription and maintaining gene expression fidelity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Moreover, HMGN1 contributes to the cellular DNA damage response by modulating the accessibility of the chromatin landscape. In this capacity, it optimizes the activation of the ATM kinase following double‐strand breaks and stimulates PARP‐1 self‐PARylation, mechanisms that are critical for genome stability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Outside the nucleus, extracellular HMGN1 serves as an alarmin by engaging Toll‐like receptor 4 on dendritic cells, thereby potentiating innate immune responses and the subsequent induction of antigen‐specific adaptive immunity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In addition, genetic associations link HMGN1 to variations in cognitive function and neuropsychiatric phenotypes"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", while its altered expression during embryogenesis affects developmental programs such as chondrogenesis—likely via modulation of key regulatory factors like Sox9."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Finally, aberrant HMGN1 expression contributes to transcriptional amplification phenomena observed in conditions such as Down syndrome and may influence tumorigenesis by impacting chromatin dynamics."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies underscore HMGN1 as a critical epigenetic regulator whose dynamic interplay with nucleosomes not only governs transcription and chromatin accessibility but also ensures an effective response to DNA damage and modulates immune as well as developmental processes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jae-Hwan Lim, Frédéric Catez, Yehudit Birger, et al. 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