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PMID:26711116
Citation |
Zhu, X, Girardo, D, Govek, EE, John, K, Mellén, M, Tamayo, P, Mesirov, JP and Hatten, ME (2016) Role of Tet1/3 Genes and Chromatin Remodeling Genes in Cerebellar Circuit Formation. Neuron 89:100-12 |
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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. |
Links |
PubMed PMC4707072 Online version:10.1016/j.neuron.2015.11.030 |
Keywords |
Animals; Brain/cytology; Brain/growth & development; Brain/metabolism; Cell Differentiation/genetics; Chromatin Assembly and Disassembly; DNA Methylation; DNA-Binding Proteins/genetics; Gene Expression Regulation, Developmental/genetics; Mice; Mice, Transgenic; Mouse Embryonic Stem Cells/cytology; Mouse Embryonic Stem Cells/metabolism; Proto-Oncogene Proteins/genetics |
Significance
Annotations
Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
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GO:0048813: dendrite morphogenesis |
ECO:0000315: |
P |
In figure 7 (C and D), Tet knockdown impairs dendritic arborization of murine cerebellar granule cells without affecting granule cell migration. |
complete | ||||
Notes
See also
References
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