Abstract
In humans and other eukaryotes, histone post-translational modifications (hPTMs) play an essential role in the epigenetic control of gene expression. In trypanosomatid parasites, conversely, gene regulation occurs mainly at the post-transcriptional level. However, our group has recently shown that hPTMs are abundant and varied in Trypanosoma cruzi, the etiological agent of Chagas Disease, signaling for possible conserved epigenetic functions. Here, we applied an optimized mass spectrometry-based proteomic workflow to provide a high-confidence comprehensive map of hPTMs, distributed in all canonical, variant and linker histones of T. cruzi. Our work expands the number of known T. cruzi hPTMs by almost 2-fold, representing the largest dataset of hPTMs available to any trypanosomatid to date, and can be used as a basis for functional studies on the dynamic regulation of chromatin by epigenetic mechanisms and the selection of candidates for the development of epigenetic drugs against trypanosomatids.
Highlights
Background & SummaryTrypanosoma cruzi, the causative agent of Chagas Disease, is a flagellated protozoan belonging to the order Kinetoplastida, family Trypanosomatidae[1]
T. cruzi passes through different hosts, including mammals and insects and, to adapt to these different environments, undergoes dramatic changes in its phenotype, which require a fine regulation of gene expression
Our group identified a plethora of 13 different histone post-translational modifications (hPTMs) types in T. cruzi epimastigotes, starting to unravel a histone code that potentially supports the existence of chromatin regulation via post-translational modification in this parasite[20]
Summary
Background & SummaryTrypanosoma cruzi, the causative agent of Chagas Disease, is a flagellated protozoan belonging to the order Kinetoplastida, family Trypanosomatidae[1]. We applied optimized sample preparation, two parallel mass spectrometry-based proteomic approaches (GeLC-MS/MS and LC-MS/MS) with complimentary sensitive/ high-resolution fragmentation techniques (CID/HCD) and de novo assisted database search (Fig. 1) to deeply profile the PTMs of T. cruzi canonical, variant and linker histones, increasing to 189 the number of hPTM sites and to 353 the number of hPTM marks described for this parasite (Fig. 2) and contributing to the hypothesis of the existence of dynamic regulation of chromatin by hPTMs in trypanosomatids.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.