title: Spectroscopic analysis of the interaction of valproic acid with histone H1 in solution and in chromatin structure.
abstract: Histone H1 is a basic chromosomal protein which links adjacent nucleosomes in chromatin structure. Valproic acid (VPA), a histone deacetylase inhibitor, is widely used as an antiepileptic drug for the treatment of various cancers. In this study the interaction between VPA and histone H1, chromatin and DNA in solution was investigated employing spectroscopic techniques. The results showed that VPA binds cooperatively to histone H1 and chromatin but exhibited very weak interaction with DNA. The association constants demonstrated higher affinity of VPA to H1 compared to chromatin. Fluorescence emission intensity was reduced by quenching value (Ksv) of 2.3 and 0.83 for H1 and chromatin respectively. VPA also altered ellipticity of chromatin and H1 at 220nm indicating increase in α-helix content of H1/chromatin proteins suggesting that the protein moiety of chromatin is the site of VPA action. Moreover, thermal denaturation revealed hypochromicity in chromatin Tm profiles with small shift in Tm values without any significant change in DNA pattern. It is concluded that VPA, apart from histone deacetylase inhibition activity, binds strongly to histone H1 in chromatin structure, demonstrating that VPA may also exert its anticancer activity by influencing chromatin proteins which opens new insight into the mechanism of VPA action.
authors.affiliation: Department of Biochemistry, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
authors.forename: Javad
authors.initials: J
authors.lastname: Sargolzaei
authors.affiliation: Department of Biochemistry, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran. Electronic address: arabbani@ut.ac.ir.
authors.forename: Azra
authors.initials: A
authors.lastname: Rabbani-Chadegani
authors.affiliation: Department of Biochemistry, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Mollaei
authors.affiliation: Department of Molecular Medicine and Biochemistry, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
authors.forename: Abdolkhalegh
authors.initials: A
authors.lastname: Deezagi
mesh_terms: D002843:Chromatin / Q000737:chemistry* / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D012996:Solutions; D013057:Spectrum Analysis; D044366:Transition Temperature; D014635:Valproic Acid / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D002843:Chromatin; D006657:Histones; D012996:Solutions; D014635:Valproic Acid; D004247:DNA
keywords: Chromatin; Histones; Spectroscopy; Valproic acid