{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:36:05Z","timestamp":1790742965070,"version":"4.1.0"},"reference-count":60,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100016880","name":"Marguerite-Marie Delacroix foundation","doi-asserted-by":"publisher","award":["FFP240064"],"award-info":[{"award-number":["FFP240064"]}],"id":[{"id":"10.13039\/100016880","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Autism Research"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Activity\u2010Dependent Neuroprotective Protein (ADNP) is a putative transcription factor that differentially interacts with proteins involved in chromatin remodeling, thereby controlling neuronal differentiation. The protein contains nine zinc fingers, a bipartite nuclear localization signal (NLS), and a homeobox domain with a heterochromatin protein 1 interaction motif, ensuring nuclear association with DNA and chromatin.\n                    <jats:italic>De novo<\/jats:italic>\n                    variants in\n                    <jats:italic>ADNP<\/jats:italic>\n                    cause autism comorbid with intellectual disability in the Helsmoortel\u2013Van der Aa syndrome. ADNP interacts with components of the SWI\/SNF in HEK293T cells but has also been reported as part of the repressive ChAHP complex in mouse embryonic stem cells. Although converging evidence suggests a role in chromatin remodeling, Hi\u2010C experiments failed to detect major alterations in 3D chromatin structure. We therefore investigated ADNP's role in epigenetic regulation and identified the chromatin scaffolding protein WDR5 and HDAC2 as interaction partners. Structural modeling revealed two N\u2010terminal methyltransferase domains, suggesting catalytic activity via SAM to SAH conversion. Immunoprecipitated fractions containing wild\u2010type ADNP exhibited methyltransferase activity, which was reduced by nonsense variants. ADNP was expressed in histone\u2010enriched cerebellar fractions in mice and a Helsmoortel\u2013Van der Aa autopsy case, with male\u2010specific reduction of the H3K79me1 modification. At the DNA level, wild\u2010type ADNP induced CpG hypermethylation. However, most variants caused CpG hypomethylation, supporting a loss\u2010of\u2010function mechanism, while NLS variants showed additional hypermethylation, suggesting a gain\u2010of\u2010function effect linked to apoptosis and microtubule transport. Taken together, we identified an ADNP\u2010WDR5\u2010HDAC2 protein complex involved in epigenetic regulation, with ADNP exhibiting methyltransferase activity in overexpression systems.\n                  <\/jats:p>","DOI":"10.1002\/aur.70132","type":"journal-article","created":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T09:40:22Z","timestamp":1761990022000},"page":"2174-2191","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["<scp>ADNP<\/scp>\n                    Exhibits Methyltransferase Activity in Overexpression Systems and Modulates\n                    <scp>DNA<\/scp>\n                    and Histone Methylation"],"prefix":"10.1002","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1888-9066","authenticated-orcid":false,"given":"Claudio Peter","family":"D'Incal","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Cognitive Genetics (COGNET), Center of Medical Genetics University of Antwerp  Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten Esther","family":"Van Rossem","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Cognitive Genetics (COGNET), Center of Medical Genetics University of Antwerp  Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Cappuyns","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Cognitive Genetics (COGNET), Center of Medical Genetics University of Antwerp  Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6713-2943","authenticated-orcid":false,"given":"Anke","family":"Van Dijck","sequence":"additional","affiliation":[{"name":"Department of Medicine and Health Sciences, Family Medicine and Population Health (FAMPOP) University of Antwerp  Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Elinck","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Cognitive Genetics (COGNET), Center of Medical Genetics University of Antwerp  Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"De Man","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Cognitive Genetics (COGNET), Center of Medical Genetics University of Antwerp  Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayu","family":"Scott","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Cognitive Genetics (COGNET), Center of Medical Genetics University of Antwerp  Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Konings","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Cognitive Genetics (COGNET), Center of Medical Genetics University of Antwerp  Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale John","family":"Annear","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Cognitive Genetics (COGNET), Center of Medical Genetics University of Antwerp  Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2024-0485","authenticated-orcid":false,"given":"R. 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