Figure 8. Proposed model of the acetylation-dependent activation of Smp14 transcription and eggshell formation.

The nuclear receptor heterodimer SmRXR1/SmNR1 binds to a specific DNA response element present in the Smp14 promoter [14] and recruits the two histone acetyltransferases SmGCN5 and SmCBP1. Chromatin is then remodeled, RNA Pol II is attracted to the promoter and transcription occurs. Synthesis of Smp14 proteins will lead to eggshell formation, which is a prerequisite for egg dissemination and granuloma formation. Interfering with the histone acetyltransferase activities of either SmCBP1 or SmGCN5 reverses chromatin decondensation, with no access for RNA Poll II. Transcription of the Smp14 gene is halted, compromising eggshell integrity, which can ultimately lead to a reduction in the transmission and immunopathology of schistosomiasis.