Epigenetic regulation of the human GDAP1 gene

Autor: Kaja Karaś, Joanna Pastwińska, Anna Sałkowska, Iwona Karwaciak, Marcin Ratajewski
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Biochemistry and Biophysics Reports, Vol 40, Iss , Pp 101827- (2024)
Druh dokumentu: article
ISSN: 2405-5808
DOI: 10.1016/j.bbrep.2024.101827
Popis: Mutations in the ganglioside-induced differentiation-associated protein 1 (GDAP1) gene are linked to Charcot–Marie–Tooth (CMT) disease, a hereditary neurodegenerative condition. The protein encoded by this gene is involved in mitochondrial fission and calcium homeostasis. Recently, GDAP1 has also been implicated in the survival of patients with certain cancers. Despite its significant role in specific cellular processes and associated diseases, the mechanisms regulating GDAP1 expression are largely unknown. Here, we show for the first time that methylation of the CpG island in the proximal promoter of the GDAP1 gene inhibits its activity. Treating cells with low GDAP1 expression using methyltransferase and HDAC inhibitors induced the expression of this gene and its encoded protein. This induction was associated with promoter demethylation and increased association of acetylated histones with the GDAP1 promoter. Thus, we identified a mechanism that could be used to manipulate GDAP1 expression.
Databáze: Directory of Open Access Journals