tHistone 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 treat-ment of various cancers. In this study the interaction between VPA and histone H1, chromatin andDNA in solution was investigated employing spectroscopic techniques. The results showed that VPAbinds cooperatively to histone H1 and chromatin but exhibited very weak interaction with DNA. Theassociation constants demonstrated higher affinity of VPA to H1 compared to chromatin. Fluorescenceemission intensity was reduced by quenching value (Ksv) of 2.3 and 0.83 for H1 and chromatin respec-tively. VPA also altered ellipticity of chromatin and H1 at 220 nm indicating increase in -helix contentof 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 inTm values without any significant change in DNA pattern. It is concluded that VPA, apart from histonedeacetylase inhibition activity, binds strongly to histone H1 in chromatin structure, demonstrating thatVPA may also exert its anticancer activity by influencing chromatin proteins which opens new insightinto the mechanism of VPA action.
