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Here, we show that\n            <jats:italic toggle=\"yes\">Atoh1-Cre<\/jats:italic>\n            \u2013mediated knockout (ACKO) of\n            <jats:italic toggle=\"yes\">Kmt2d<\/jats:italic>\n            encoding the lysine methyltransferase KMT2D (MLL4) in cerebellar GC lineage inhibits the transition of GC progenitors to GCs while cell non-autonomously affecting other cerebellar cells.\n            <jats:italic toggle=\"yes\">Kmt2d<\/jats:italic>\n            ACKO impaired cerebellum-associated behaviors and caused facial peculiarity, microcephaly, and reduced body size in mice. KMT2D temporally activated neuronal differentiation programs in cerebellar GCs. KMT2D-mediated activation of the key neuronal transcription factor genes\n            <jats:italic toggle=\"yes\">En2<\/jats:italic>\n            ,\n            <jats:italic toggle=\"yes\">Pax6<\/jats:italic>\n            , and\n            <jats:italic toggle=\"yes\">Myt1l<\/jats:italic>\n            via super-enhancer\/enhancer programming was critical for GC differentiation. These findings reveal a unique epigenetic mechanism in which KMT2D temporally orchestrates gene expression required for cerebellar GC differentiation by programming neuronal enhancers.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adu7174","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T17:58:32Z","timestamp":1758909512000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":3,"title":["KMT2D temporally activates neuronal transcriptional factor genes to mediate cerebellar granule cell differentiation"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5922-2164","authenticated-orcid":true,"given":"Shilpa S.","family":"Dhar","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, 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