Summary
Although mechanisms underlying early steps in cerebellar development are known,
evidence is lacking on genetic and epigenetic changes during the establishment of the
synaptic circuitry. Using metagene analysis, we report pivotal changes in multiple
reactomes of epigenetic pathway genes in cerebellar granule cells (GCs) during circuit
formation. During this stage, Tet genes are up-regulated and vitamin C activation of Tet
enzymes increases the levels of 5-hydroxymethylcytosine (5hmC) at exon start sites of
up-regulated genes, notably axon guidance genes and ion channel genes. Knockdown of
Tet1 and Tet3 by RNA interference in ex
vivo cerebellar slice cultures inhibits dendritic arborization of developing
GCs, a critical step in circuit formation. These findings demonstrate a role for Tet genes
and chromatin remodeling genes in the formation of cerebellar circuitry.
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