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Histone modification is one of the attractive targets for epigenetic studies. However, current methods to extract chromatin-associated proteins for western blot of histone modification have some weaknesses such as the loss of housekeeping proteins. In this study, we are presenting a simple method to isolate nuclear protein for studying histone modification by immunoblotting with housekeeping proteins. This method provided high protein concentration from minute tissue samples and importantly, it allowed us to detect acetylated histones together with internal control proteins such as β actin. [ J Adv Biotechnol Exp Ther 2018; 1(1.000): 25-28]