Interrogating the nuclear genome organization in Trypnanosoma cruzi replicative and non-replicative life forms by using high-throughput chromosome conformation capture (Hi-C) approach

Abstract

This proposal is designed to address nuclear three-dimensional features of two life forms of the parasite Trypanosoma cruzi, and to investigate its probable impacts on different aspects of T. cruzi biology. Gene expression in trypanosomes is broadly determined by post-transcriptional mechanisms, however, a significant decrease in global transcription has been observed if comparing their life forms, suggesting some layer of transcription regulation. Additionally, T. cruzi are subjected to many epigenetic changes (e.g., histone PTMs, nucleosome differential occupancy, different levels of open chromatin, etc) that changes along parasite life and cell cycle. The 3D genome organization was shown to be important on monogenic expression of antigenic variant surface glycoproteins in T. brucei. We hypothesize that the 3D genome organization in the T. cruzi can also be one additional layer of gene expression regulation. Thus, we propose to standardize and obtain high-throughput chromosome conformation capture (Hi-C) assays of T. cruzi to characterize their 3D landscape of chromatin in two life forms. For this proposal, bioinformatic pipelines will be applied and data will be explored preliminary to further elucidate possible interplays between the nuclear architecture and epigenomic profile in T.cruzi. (AU)