TFIIE orchestrates the recruitment of the TFIIH kinase module at promoter before release during transcription.

In eukaryotes, the general transcription factors TFIIE and TFIIH assemble at the transcription start site with RNA Polymerase II. However, the mechanism by which these transcription factors incorporate the preinitiation complex and coordinate their action during RNA polymerase II transcription remains elusive. Here we show that the TFIIEα and TFIIEß subunits anchor the TFIIH kinase module (CAK) within the preinitiation complex. In addition, we show that while RNA polymerase II phosphorylation and DNA opening occur, CAK and TFIIEα are released from the promoter. This dissociation is impeded by either ATP-γS or CDK7 inhibitor THZ1, but still occurs when XPB activity is abrogated. Finally, we show that the Core-TFIIH and TFIIEß are subsequently removed, while elongation factors such as DSIF are recruited. Remarkably, these early transcriptional events are affected by TFIIE and TFIIH mutations associated with the developmental disorder, trichothiodystrophy.

[Myocardial cellular damage and the activity of the mitochondrial ATP synthase in rats infected with a Colombian strain of Trypanosoma cruzi]. / Lesión celular del miocardio y actividad de la ATPsintasa mitocondrial en ratas infectadas con una cepa colombiana de Trypanosoma cruzi.

INTRODUCTION: Chagas disease is the main cause of cardiomyopathy in endemic regions of Latin America. Alterations in the cardiac mitochondrial energy metabolism caused by Trypanosoma cruzi can be involved in the development of this cardiomyopathy during the course of Chagas disease. OBJECTIVE: The cellular injury of the rat myocardium was investigated in rats infected with the Colombian Mg8 strain of Trypanosoma cruzi. The activity of mitochondrial ATP synthase was measured to determine the relationship heart damage with the energy metabolism. MATERIALS AND METHODS: Two groups of five rats each were infected with tripomastigotes, with 1 group of 6 rats serving as controls. The course of infection was characterized by parasitological, histopathological and molecular studies. The mitochondrial ATP synthase activity of the myocardium was evaluated in all rats. RESULTS: Peak parasitaemia (day 26 post infection) and the time of parasite clearance from circulating blood (day 60 post infection) were determined for acute and chronic phase models. The histopathological and molecular results showed that the Colombian Mg8 strain has tropism to the cardiac tissue and causes considerable cellular injury of the myocardium in rats during both phases. Despite the lesions observed in infected rats, no statistical difference in the activity of the mitochondrial ATPsynthase was observed between them and the non-infected rats. CONCLUSION: Mitochondrial energy metabolism of the cardiomyocites does not appear to change during cellular injury of rat myocardium associated with infection by the Colombian Mg8 T. cruzi strain.