VSG gene 118 is transcribed from a cotransposed pol I-like promoter

To understand the control of differential variant cell surface glycoprotein (VSG) gene expression in T. brucei, we studied VSG gene and expression site transcription regulation. We show that the interchromosomal duplicative transposition of VSG gene 118, on an unusually large transposed segment, results in the transcriptional activation of a cotransposed RNA polymerase I-like (pol I) promoter, from which the VSG gene is transcribed. Transcription of VSG genes by pol I can therefore be regulated by DNA rearrangements that affect positional control of gene expression. A 5' cap is added in trans to the pol I-derived pre-mRNA, by addition of a pol II-derived 35 nucleotide mini-exon. A second gene (ESAG1) is located 25 kb upstream of the VSG 118 gene and is also transcribed. This expression site therefore contains at least two independently regulated genes. We discuss the putative importance of a nucleolar location for VSG gene and expression site transcription regulation.