Injury-Associated Differential Regulation of Histone Expression and Modification in the Thymus of Mice

Abstract

One of the key events in the regulation of gene expression is chromatin remodeling involving histone regulation. We investigated the effects of burns on the expression of histone that might be associated with altered molecular and pathological profiles in the thymus. A markedly decreased expression of histone variant H2A.1 mRNA was identified in the thymus after burn during a differential display experiment. Subsequently, we examined the histone expression (mRNA and protein) and posttranslational modification in the thymus after burn. Also, changes in proliferating cell nuclear antigen (PCNA), a central molecule in chromatin assembly, was examined. Reverse-transcription polymerase chain reaction analysis revealed a transient decrease in the expression of several histone variants (H2A.1, H1(r1), H3-B, H3-1, and H4-D) mRNAs in the thymus at 1 day after burn. A decrease in histone subtypes H2A, H2B, H3, and H4, but not H1, was demonstrated 1 and 3 days after burn according to the results of Western blot. Furthermore, there were different levels of decreases in acetylated and dimethylated forms of histone H3 1 and 3 days after burn. In addition, decreased levels of PCNA were evident in the thymus 1 day after burn. Changes in the expression of histones and PCNA may reflect mere decrease in proliferating cells and/or a reorganization of the chromatin structure associated with altered transcriptional activities, eventually contributing to the phenotypic changes in the thymus after burn.