Abstract
Valproic acid/sodium valproate (VPA), a drug originally prescribed as an anticonvulsant, has been widely reported to act on epigenetic marks by inducing histone acetylation, affecting the DNA and histone methylation status, and altering the expression of transcription factors, thus leading to modulation of gene expression. All these epigenetic changes have been associated with chromatin remodeling effects. The present minireview briefly reports the main effects of VPA on chromatin and image analysis and Fourier transform infrared (FTIR) microspectroscopy in association with molecular biology methodological approaches to investigate the VPA-induced changes in chromatin structure and at the higher-order supraorganizational level.
Highlights
Chromatin, which in eukaryotic cells is a complex structure containing DNA, histones, non-histone proteins and RNA, has a dynamic organization essential for its normal physiological performance
Drugs that inhibit histone deacetylases (HDACi), facilitate the access of acetyl groups to histones or interfere with the activity of methyltransferases that control the methylation status of DNA and histones, have a role affecting gene expression that is generally accompanied by chromatin remodeling
Valproic acid has been found to induce chromatin decondensation that lasts longer than the time assigned to promote histone acetylation. This finding suggested that valproic acid (VPA) could affect the methylation status of DNA and histones, which was confirmed in several cell types, including tumor cells (Detich et al, 2003; Milutinovic et al, 2007; Marinova et al, 2011; Palsamy et al, 2014; Rocha et al, 2019)
Summary
Chromatin, which in eukaryotic cells is a complex structure containing DNA, histones, non-histone proteins and RNA, has a dynamic organization essential for its normal physiological performance. Drugs that inhibit histone deacetylases (HDACi), facilitate the access of acetyl groups to histones or interfere with the activity of methyltransferases that control the methylation status of DNA and histones, have a role affecting gene expression that is generally accompanied by chromatin remodeling One example of such a drug is valproic acid (VPA), which was originally prescribed for the treatment of seizure disorders and was subsequently revealed to be a potent epigenetic agent. Valproic acid has been found to induce chromatin decondensation that lasts longer than the time assigned to promote histone acetylation This finding suggested that VPA could affect the methylation status of DNA and histones, which was confirmed in several cell types, including tumor cells (Detich et al, 2003; Milutinovic et al, 2007; Marinova et al, 2011; Palsamy et al, 2014; Rocha et al, 2019). Other effects not directly affecting epigenetic markers and unknown until recently, have been proposed after the analysis of mixtures of VPA and DNA and VPA and histones revealed molecular interactions between VPA and chromatin components in vitro (Sargolzaei et al, 2017; Vidal and Mello, 2020)
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