Faculty of 1000 evaluation for Role of tet1/3 genes and chromatin remodeling genes in cerebellar circuit formation [dataset]

Stephanie Gupton, Shalini Menon
2018 F1000 - Post-publication peer review of the biomedical literature   unpublished
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 5hydroxymethylcytosine (5hmC) at exon
more » ... 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.
doi:10.3410/f.726044443.793552037 fatcat:ntejim3xxfhmpaclobp6uzpsve