RhoB, a member of the Rho family of small GTPases, regulates the organization of the actin cytoskeleton, malignant transformation, and genotoxic stress-induced signaling. In order to characterize epigenetic regulation of RhoB transcription during aging, the mRNA levels of RhoB were investigated using various mouse tissues of different ages. Bisulfite sequencing revealed that the CpG dinucleotide methylation patterns of the RhoB promoter region were not altered in skeletal muscle and lung during aging. ChIP analysis showed that levels of histone H3 and H4 acetylation were reduced in a tissue-specific manner during aging due to direct HDAC I binding. Histone H3 lysine 9 trimethylation level and deposition of HP 10 increased in RhoB promoter during aging, whereas historic H3 lysine 4 dimethylation level gradually decreased. It was concluded that mouse RhoB transcription is epigenetically regulated in a tissue-specific manner during aging by histone modification, but not by CpG methylation. (C) 2007 Elsevier Inc. All rights reserved.