Role of Tet1/3 Genes and Chromatin Remodeling Genes in Cerebellar Circuit Formation.

Neuron
Authors
Keywords
Abstract

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 upregulated and vitamin C activation of Tet enzymes increases the levels of 5-hydroxymethylcytosine (5hmC) at exon start sites of upregulated genes, notably axon guidance genes and ion channel genes. Knockdown of Tet1 and Tet3 by RNAi 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.

Year of Publication
2016
Journal
Neuron
Volume
89
Issue
1
Pages
100-12
Date Published
2016 Jan 06
ISSN
1097-4199
URL
DOI
10.1016/j.neuron.2015.11.030
PubMed ID
26711116
PubMed Central ID
PMC4707072
Links
Grant list
R01 GM074024 / GM / NIGMS NIH HHS / United States
U54HG006093 / HG / NHGRI NIH HHS / United States
R01 NS051778 / NS / NINDS NIH HHS / United States
R01CA154480 / CA / NCI NIH HHS / United States
U24 CA194107 / CA / NCI NIH HHS / United States
U54 HG006093 / HG / NHGRI NIH HHS / United States
U54CA112962 / CA / NCI NIH HHS / United States
R01NS051778 / NS / NINDS NIH HHS / United States
R01109467 / PHS HHS / United States
P30 CA023100 / CA / NCI NIH HHS / United States
R01 CA154480 / CA / NCI NIH HHS / United States
R21 NS093540 / NS / NINDS NIH HHS / United States
U54 CA112962 / CA / NCI NIH HHS / United States
R01 CA121941 / CA / NCI NIH HHS / United States
R01GM074024 / GM / NIGMS NIH HHS / United States