Identification of Rpd3 as a novel epigenetic regulator of Drosophila FIG 4, a Charcot-Marie-Tooth disease-causing gene
| Autor: | Ryosuke Kowada, Atsushi Nikaido, Hiroshi Kimura, Yuuka Muraoka, Hideki Yoshida, Masamitsu Yamaguchi |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Gene knockdown General Neuroscience Neuromuscular Junction Regulator Histone Deacetylase 1 Compound eye Motor Activity Biology HDAC1 Epigenesis Genetic Cell biology Synapse Pathogenesis 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Charcot-Marie-Tooth Disease Gene Knockdown Techniques Animals Drosophila Proteins Drosophila Epigenetics Gene 030217 neurology & neurosurgery |
| Zdroj: | NeuroReport. |
| ISSN: | 0959-4965 |
| DOI: | 10.1097/wnr.0000000000001636 |
| Popis: | Mutations in the factor-induced-gene 4 (FIG 4) gene are associated with multiple disorders, including Charcot-Marie-Tooth disease (CMT), epilepsy with polymicrogyria, Yunis-Varón syndrome and amyotrophic lateral sclerosis. The wide spectrum of disorders associated with FIG 4 may be related to the dysregulated epigenetics. Using Gene Expression Omnibus, we found that HDAC1 binds to the FIG 4 gene locus in the genome of human CD4+ T cells. Rpd3 is a well-known Drosophila homolog of human HDAC1. We previously established Drosophila models targeting Drosophila FIG 4 (dFIG 4) that exhibited defective locomotive ability, abnormal synapse morphology at neuromuscular junctions, enlarged vacuoles in the fat body and aberrant compound eye morphology. Genetic crossing experiments followed by physiological and immunocytochemical analyses revealed that Rpd3 mutations suppressed these defects induced by dFIG 4 knockdown. This demonstrated Rpd3 to be an important epigenetic regulator of dFIG 4, suggesting that the inhibition of HDAC1 represses the pathogenesis of FIG 4-associated disorders, including CMT. Defects in epigenetic regulators, such as HDAC1, may also explain the diverse symptoms of FIG 4-associated disorders. |
| Databáze: | OpenAIRE |
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