{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CHD2 encodes an ATP‐dependent chromatin remodeler that plays diverse roles in regulating chromatin structure and thereby modulates multiple fundamental cellular processes. In the context of the DNA damage response, CHD2 is rapidly recruited—via PARP1‐dependent poly(ADP‐ribosyl)ation—to sites of double‐strand DNA breaks, where it facilitates chromatin expansion and promotes the deposition of the histone variant H3.3, actions that are critical for proper repair and the stabilization of replication forks."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the nervous system, CHD2 is highly expressed in radial glial progenitors, where it sustains self‐renewal and regulates neuronal differentiation through direct modulation of key factors such as REST. Disruption of CHD2 function—whether by de novo loss‐of‐function mutations, inherited variants, or chromosomal rearrangements—leads to a broad spectrum of neurodevelopmental impairments. These include early onset epileptic encephalopathies, generalized and photosensitive epilepsies (with seizure types ranging from myoclonic to atonic), intellectual disability, and even behavioral abnormalities such as those seen in autism spectrum disorders and schizophrenia."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "14"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its critical functions in neuronal development, CHD2 contributes to the maintenance of genomic integrity and the regulation of gene transcription in other tissues. Its role as a tumor suppressor is evidenced by its involvement in hematopoietic stem cell differentiation and in protecting against lymphomagenesis and glomerulopathy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": " In addition, CHD2 activity is subject to regulation by noncoding RNAs; for instance, the long noncoding RNA Chaserr acts in cis to fine‐tune CHD2 expression levels, underscoring the importance of precise dosage for proper cellular function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n At the biochemical level, CHD2’s remodeling activity—mediated by distinct regulatory domains that coordinate its ATPase function and substrate specificity—enables the assembly of chromatin into periodic arrays, a structural reorganization fundamental for transcriptional regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": " Moreover, CHD2 has been implicated in the regulation of viral gene transcription, acting as a positive effector of HIV-1 expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, emerging evidence links altered CHD2 expression with changes in tissue homeostasis and disease susceptibility beyond the nervous system. For example, deregulation of CHD2 has been observed in contexts ranging from chronic lymphocytic leukemia and obesity-related traits to pregnancy-induced modifications in the breast that may influence cancer risk."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "20", "end_ref": "25"}]}, {"type": "t", "text": " In one illustrative case, chromosomal disruption of CHD2 was associated with scoliosis and developmental delay, further emphasizing its pleiotropic impact on human phenotype."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "26"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, CHD2 functions as a master regulator of chromatin dynamics, integrating signals from DNA damage, developmental cues, and transcriptional networks to maintain genomic integrity, regulate gene expression, and ensure proper cellular differentiation. Disruption of CHD2—through mutation, altered regulation, or chromosomal breakage—can thus lead to a spectrum of pathologies, ranging from epileptic encephalopathies and neurodevelopmental disorders to cancer and metabolic dysfunction.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Martijn S Luijsterburg, Inge de Krijger, Wouter W Wiegant, et al. 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