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Nevertheless, the precise function of the RNA demethylase Fto in the cerebellum is still uncertain.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>An <jats:italic>Fto<\/jats:italic> knockout (<jats:italic>Fto<\/jats:italic>\n              <jats:sup>\n                <jats:italic>KO<\/jats:italic>\n              <\/jats:sup>) mouse model was generated to investigate the role of <jats:italic>Fto<\/jats:italic> in cerebellar development. Cerebellar function was assessed using the behavioral tests and Nissl staining. Immunofluorescence was performed to detect molecular expression levels and subcellular localization. Dot blot, m<jats:sup>6<\/jats:sup>A-RIP-seq, ATAC-seq and CUT&amp;Tag-seq were used to confirm m<jats:sup>6<\/jats:sup>A levels and chromatin accessibility. Co-IP was employed to test molecular interactions.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>\n              <jats:italic>Fto<\/jats:italic>\n              <jats:sup>\n                <jats:italic>KO<\/jats:italic>\n              <\/jats:sup> mice exhibited cerebellar ataxia, including tremors and abnormal gait patterns. Reduced FTO expression at embryonic day 13.5 (E13.5) and postnatal day 3 (P3) stages resulted in increased TUJ1 expression, as well as reductions in neuronal functional genes (<jats:italic>Map2<\/jats:italic>) and self-renewal genes (<jats:italic>Sox2<\/jats:italic>, <jats:italic>Sox9<\/jats:italic>, <jats:italic>Nestin<\/jats:italic> and <jats:italic>Pax6<\/jats:italic>). Mechanistically, <jats:italic>Kat8<\/jats:italic> upregulation was linked to the high m<jats:sup>6<\/jats:sup>A levels regulated by <jats:italic>Fto<\/jats:italic> loss. Furthermore, IGF2BP3 specifically recruited acetyltransferase KAT8 to control gene transcription during early cerebellar development by regulating H4K16ac modification, which alters chromatin accessibility in neural developmental pathways.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>In summary, <jats:italic>Fto<\/jats:italic>\n              <jats:sup>\n                <jats:italic>KO<\/jats:italic>\n              <\/jats:sup>-induced <jats:italic>Kat8<\/jats:italic> upregulation in an m<jats:sup>6<\/jats:sup>A-dependent manner resulted in enhanced KAT8 recruitment by IGF2BP3, which improved chromatin accessibility and H4K16ac modification, thereby promoting cerebellar developmental dysfunction.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12929-025-01176-0","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T14:55:38Z","timestamp":1756479338000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Fto-mediated m6A modification is essential for cerebellar development through regulating epigenetic reprogramming"],"prefix":"10.1186","volume":"32","author":[{"given":"Jing","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyue","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jincheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiujuan","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiafeng","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingxia","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoi-Hung","family":"Cheung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9913-9077","authenticated-orcid":false,"given":"Boxian","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,29]]},"reference":[{"key":"1176_CR1","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1002\/dneu.20875","volume":"72","author":"M Hibi","year":"2012","unstructured":"Hibi M, Shimizu T. 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