Repression and reactivation of the variant surface glycoprotein gene in Trypanosoma brucei.

Rapid repression of variant surface glycoprotein (VSG) synthesis is an early event during the in vitro transformation of Trypanosoma brucei from coated bloodstream forms to uncoated procyclic cells. Repression occurs at the transcriptional level and is triggered by the combined action of two signals: a reduction in temperature from 37 to 27 degrees C and the addition of the citric acid cycle intermediates citrate and cis-aconitate. It is shown that synthesis of VSG mRNA can be reactivated up to 8 h after triggering differentiation by releasing either one or both of the signals. After 30 h repression is irreversible. The results suggest that transformation of bloodstream forms to procyclic cells proceeds through a reversible phase to an irreversible committed state. A reversible repression of VSG mRNA synthesis is also observed upon inhibition of protein synthesis in bloodstream forms at 37 degrees C.