Reciprocal regulation of gene expression by Ephedra herba in mouse brain

Although Ephedra herba has been used to treat a variety of diseases, the molecular mechanism has not been defined clearly. To identify the molecular events, a microarray analysis was conducted using the brain tissue of mice orally administered aqueous extracts of Ephedra herba, in which the expression level of many genes was altered depending on the duration of treatment time. In particular, temporal changes in the expressions of genes can be classified into two major reciprocal patterns in which 175 and 282 genes were included in pattern 1 and 2, respectively. Classification based on gene ontology revealed different functional implications of genes between temporal pattern 1 and 2. Through promoter analysis of temporally co-expressed genes, putative co-regulated genes could be segregated based on the similarity of the transcription factor binding sites (TFBS). Interestingly, two temporal patterns were associated with different sub-classes of TFBS similarity, which implies the presence of dual regulatory mechanisms. Finally, through interaction analysis, core node genes that could interact with many other nodes were identified. By integrating the interaction information with promoter clustering, temporally co-regulated key components could be selected in mouse brain after administration of Ephedra herba.