Identification of Rpd3 as a novel epigenetic regulator of Drosophila FIG 4, a Charcot-Marie-Tooth disease-causing gene.
Journal
Neuroreport
ISSN: 1473-558X
Titre abrégé: Neuroreport
Pays: England
ID NLM: 9100935
Informations de publication
Date de publication:
05 05 2021
05 05 2021
Historique:
entrez:
14
4
2021
pubmed:
15
4
2021
medline:
29
1
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33850086
doi: 10.1097/WNR.0000000000001636
pii: 00001756-202105010-00007
doi:
Substances chimiques
Drosophila Proteins
0
HDAC1 protein, Drosophila
EC 3.5.1.98
Histone Deacetylase 1
EC 3.5.1.98
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
562-568Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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