Work

Epigenetic regulation of the human GDAP1 gene

Year: 2024

Type: article

Abstract: 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. • A CpG island was identified in the proximal GDAP1 promoter. • In vitro methylation inhibits GDAP1 promoter activity. • A DNA methyltransferase inhibitor induces GDAP1 expression and decreases methylation of the identified CpG island. • An HDAC inhibitor increases GDAP1 expression and enhances the association of acetylated histones with the gene promoter. • Human GDAP1 is epigenetically regulated through sequences located in the basal promoter.

Source: Biochemistry and Biophysics Reports

DOI: 10.1016/j.bbrep.2024.101827

Authors: Kaja Karaś, Joanna Pastwińska, Anna Sałkowska, Iwona Karwaciak, Marcin Ratajewski

Institutions: Institute for Medical Biology, Polish Academy of Sciences

Language: English

Topic: Epigenetics and DNA Methylation

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,540