Evaluation of Schistosoma mansoni retinoid X receptor (SmRXR1 and SmRXR2) activity and tissue distribution

Recently, we reported the identification of cDNA's encoding retinoid X rece ptor (RXR) homologues in Schistosoma mansoni. RXRs are known to be involved in the regulation of genes important for homeostasis and development. Prev ious studies indicated that SinRXR1 plays a role in the regulation of the f emale-specific gene, p14. Herein, we report that SmRXR2 also binds to cis-e lements present in the p 14 upstream region when evaluated in yeast reporte r strains. Sin RXR2 shows a pattern of recognition of cis-sequences present in the p14 gene upstream region different than SmRXR1. However, the SmRXR2 C (DNA binding) domain binds promiscuously in electrophoretic mobility shi ft assays to cis-elements of the p14 upstream region. The SmRXRs differ in their ability to activate transcription. The N-terminal A/B domain of SinRX R1 is necessary and sufficient for autonomous transcription activation func tion (AF) in yeast. SmRXR2 does not exhibit an equivalent autonomous AF. Sm RXR1 and SmRXR2 fail to dimerize when investigated both in the yeast two-hy brid system and in immunoprecipitation experiments. In situ hybridization e xperiments using paraffin sections of adult worms demonstrate that SmRXR1 a nd SmRXR2 exhibit both common and unique cell type distribution which indic ates that SmRXR1 and SmRXR2 both play a role in regulating gene expression in certain cells., yet each plays a distinct role in modulating the express ion of genes in other cell types. Both SmRXR1 and SmRXR-2 localize to vitel line cells. These studies provide a solid basis for improving our understan ding of RXRs and their importance in female-specific gene regulation. (C) 2 001 Elsevier Science B.V. All rights reserved.