Unusual histone modifications in Trypanosoma brucei

Abstract

To start to understand the role of chromatin structure in regulating transcription in trypanosomes, we analyzed covalent modifications on the four core histones of Trypanosoma brucei. We found unusually few modifications in the N-terminal tails, which are abundantly modified in other organisms and whose sequences, but not composition, are highly divergent in trypanosomes. In contrast, the C-terminal region of H2A appears to be hyper-acetylated. Surprisingly, the N-terminal alanines of H2A, H2B, and H4, were mono-methylated, a modification that has not been described previously for histones. Possible functions and evolutionary explanations for these unusual histone modifications are discussed.

Bromodomains in Protozoan Parasites: Evolution, Function, and Opportunities for Drug Development

“…Moreover, their histone sequences and the PTMs that decorate them deviate from what is observed in other eukaryotes (68)(69)(70)(71)(72). For example, histone H3 is relatively free of acetylation, the majority of modifications that have been identified are found on H4, and the C-terminal tail of histone H2A is heavily acetylated in T. brucei (71). Nevertheless, the kinetoplastids clearly use histone acetylation to regulate synthesis of the polycistronic transcripts (73,74).…”

“…Regulation of gene expression appears to be primarily posttranscriptional, via modulation of the splicing machinery that generates the mature mRNAs (67). Moreover, their histone sequences and the PTMs that decorate them deviate from what is observed in other eukaryotes (68)(69)(70)(71)(72). For example, histone H3 is relatively free of acetylation, the majority of modifications that have been identified are found on H4, and the C-terminal tail of histone H2A is heavily acetylated in T. brucei (71).…”

Histone H4 lysine 14 acetylation in Leishmania donovani is mediated by the MYST-family protein HAT4

“…1a), and therefore the histone PTMs are likely to be conserved as well. PTMs in T. brucei and T. cruzi histones have mainly been identified by MS analysis (da Cunha et al, 2006;Janzen et al, 2006;Mandava et al, 2007). Mature histones lack the first methionine residue.…”

“…Analysis of PTMs on the N-terminal tails of histones in Trypanosoma brucei and Trypanosoma cruzi (da Cunha et al, 2006;Janzen et al, 2006;Mandava et al, 2007) has revealed that H4 is heavily acetylated and methylated in its N-terminal tail, and that the H3 tail carries several modifications as well. In contrast to other eukaryotes, the H2A and H2B N-terminal tails have very few modifications, while the H2A C-terminal tail is heavily modified (Janzen et al, 2006;Mandava et al, 2007).…”

“…Analysis of PTMs on the N-terminal tails of histones in Trypanosoma brucei and Trypanosoma cruzi (da Cunha et al, 2006;Janzen et al, 2006;Mandava et al, 2007) has revealed that H4 is heavily acetylated and methylated in its N-terminal tail, and that the H3 tail carries several modifications as well. In contrast to other eukaryotes, the H2A and H2B N-terminal tails have very few modifications, while the H2A C-terminal tail is heavily modified (Janzen et al, 2006;Mandava et al, 2007). A comparison of the sequences of histones H2A, H2B, H3 and H4 of Leishmania donovani (Tritryp GeneDB; GenBank accession nos JF742060 and JF742061) with those of other Leishmania species as well as Trypanosoma species El-Sayed et al, 2005;Ivens et al, 2005;Peacock et al, 2007) reveals that the tails of H2A, H2B, H3 and H4 are highly conserved among trypanosomatids (Fig.…”