Trypanosoma brucei variant surface
glycoprotein expression sites are interesting examples of genomic
loci under complex epigenetic control. In the infectious bloodstream
stage, only one of about 20 expression sites is actively transcribed.
In the Tsetse midgut (procyclic) stage, chromatin remodeling silences
all expression sites. We have begun to explore the function of one of
the expression-site-associated genes, ESAG8. Gene knockout
experiments implied that ESAG8 is essential. ESAG8 is present at a
very low level and apparently accumulates in the nucleolus. A
32-amino-acid domain, which contains a putative bipartite nuclear
localization signal (NLS), is both necessary and sufficient to target
fusions of ESAG8, with Aequorea victoria green fluorescent protein,
to the trypanosome nucleolus. This same sequence functioned only as
an NLS in mammalian cells, supporting the idea that nucleolar
accumulation requires specific interactions. These results have
implications for models of ESAG8 function.