Stage-specific transcription activator ESB1 regulates monoallelic antigen expression in Trypanosoma brucei

Journal article

The kinetochore is the macromolecular protein machine that drives chromosome segregation in eukaryotes. In an evolutionarily divergent group of organisms called kinetoplastids, kinetochores are built using a unique set of proteins (KKT1–25 and KKIP1–12). KKT23 is a constitutively localized kinetochore protein containing a C-terminal acetyltransferase domain of unknown function. Here, using X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy, we have determined the structure and dynamics of the KKT23 acetyltransferase domain from Trypanosoma brucei and found that it is structurally similar to the GCN5 histone acetyltransferase domain. We find that KKT23 can acetylate the C-terminal tail of histone H2A and that knockdown of KKT23 results in decreased H2A acetylation levels in T. brucei. Finally, we have determined the crystal structure of the N-terminal region of KKT23 and shown that it interacts with KKT22. Our study provides important insights into the structure and function of the unique kinetochore acetyltransferase in trypanosomes.

Authors: López-Escobar, L; Hänisch, B; Halliday, C; Ishii, M; Akiyoshi, B

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: Nature Microbiology
• Volume: 7
• Issue: 8
• Pages: 1280-1290
• Publication date: 2022-07-25
• DOI: 10.1038/s41564-022-01175-z
• EISSN: 2058-5276
• ISSN: 2058-5276
• Language: English
• Keywords: Gene expression; Gene; RNA; Molecular biology; Biology; Transcription (linguistics); Antigenic variation; Activator (genetics); RNA polymerase II; Promoter; RNA polymerase; Trypanosoma brucei; Transcription factor; Cell biology; Genetics