KMT2D temporally activates neuronal transcriptional factor genes to mediate cerebellar granule cell differentiation.

ABSTRACT: Spatiotemporal gene expression is the fundamental feature of cellular differentiation, including neuron differentiation. The epigenetic mechanism underlying spatiotemporal gene regulation during in vivo neuron differentiation remains largely unknown. Granule cells (GCs) constitute the vast majority of neurons in the cerebellum, which contains most of neurons in the brain. Here, we show that Atoh1-Cre-mediated knockout (ACKO) of Kmt2d 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. Kmt2d ACKO impaired cerebellum-associated behaviors and caused facial peculiarity, microcephaly, and reduced body size in mice. KMT2D temporally activated

SUBMITTER: Dhar SS 

PROVIDER: S-EPMC12467062 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature