Histone acetylation is suggested to regulate gene expression in the TCR loci. Using R2CD3 mouse model, we previously showed that germline transcription of the TCRP chain gene is discrete between 5'Vbeta regions and Dbeta-Jbeta-Cbeta clusters plus Vbeta14 region. In this study, we investigated a role of histone H3 acetylation in transcriptional regulation of the TCRbeta locus. Our results showed that DN-DP transition is accompanied by significant promotion of histone H3 acetylation in both Dbeta-Jbeta-Cbeta cluster and Vbeta14 region, correlating with up-regulation of germline transcription. Surprisingly, termination of germline transcription of the 5'Vbeta regions was inversely correlated with histone H3 hyperacetylation. Moreover, histone H3 acetylation showed equivalent level in both functionally rearranged Vbeta region with active transcription and unrearranged Vbeta region without transcription in mature T cells. These results suggest that histone acetylation is not a sole limiting factor in both terminating germline Vbeta transcription during DN-DP transition and maintaining functionally rearranged Vbeta gene expression. (C) 2002 Elsevier Science (USA). All rights reserved.