Leaky Transcription of Variant Surface Glycoprotein Gene Expression Sites in Bloodstream African Trypanosomes

We have cloned the region spanning the putative promoter from two variant surface glycoprotein gene expression sites that are at each end of chromosome M4 of Trypanosoma brucei IsTat 7. Both expression sites contain a retroposon-like sequence (ESR) pseudogene whose 3' end is approximately 30 bp upstream of the putative expression site promoter. The ESRs from both expression sites share considerable sequence homology and are related to LINE-like elements, especially the T. brucei ingi retroposon. Other ESRs are located on large, but not intermediate or mini-, chromosomes in the IsTaR 1 serodeme, and the total copy number is 10 to 20, similar to that estimated for variant surface glycoprotein expression sites. No DNA rearrangements in the vicinity of the ESR and putative expression site promoter were detected following antigenic switches in the IsTaR 1 serodeme. ESR transcripts are present in bloodstream, but not procyclic, forms. Variation in transcript size and sequence between bloodstream variant antigenic types implies that only the ESR from the active expression site is transcribed. This pattern of expression reflects that of sequences downstream of the putative expression site promoter, suggesting that the region of coordinately controlled expression extends upstream of this promoter.

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Transcriptional regulation of metacyclic variant surface glycoprotein gene expression during the life cycle of Trypanosoma brucei.

Molecular and Cellular Biology ◽

10.1128/mcb.15.11.5945 ◽

1995 ◽

Vol 15 (11) ◽

pp. 5945-5956 ◽

Cited By ~ 33

Author(s):

S V Graham ◽

J D Barry

Keyword(s):

Gene Expression ◽

Transcriptional Regulation ◽

Life Cycle ◽

Life Cycle Stage ◽

Surface Glycoprotein ◽

Variant Surface Glycoprotein ◽

Mammalian Host ◽

Dependent Manner ◽

African Trypanosomes ◽

Specific Subset

In antigenic variation in African trypanosomes, switching of the variant surface glycoprotein (VSG) allows evasion of the mammalian host immune response. Trypanosomes first express the VSG in the tsetse fly vector, at the metacyclic stage, in preparation for transfer into the mammal. In this life cycle stage, a small, specific subset (1 to 2%) of VSGs are activated, and we have shown previously that the system of activation and expression of metacyclic VSG (M-VSG) genes is very different from that used for bloodstream VSG genes (S.V. Graham, K.R. Matthews, P.G. Shiels, and J.D. Barry, Parasitology 101:361-367, 1990). Now we show that unlike other trypanosome genes including bloodstream VSG genes, M-VSG genes are expressed from promoters subject to exclusively transcriptional regulation in a life cycle stage-dependent manner. We have located an M-VSG gene promoter, and we demonstrate that it is specifically up-regulated at the metacyclic stage. This is the first demonstration of gene expression being regulated entirely at the level of transcription among the Kinetoplastida; all other protein-coding genes examined in these organisms are, at least partly, under posttranscriptional control. The distinctive mode of expression of M-VSG genes may be due to a stochastic mechanism for metacyclic VSG activation.

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Co-duplication of a Variant Surface Glycoprotein Gene and Its Promoter to an Expression Site in African Trypanosomes

Journal of Biological Chemistry ◽

10.1074/jbc.272.39.24637 ◽

1997 ◽

Vol 272 (39) ◽

pp. 24637-24645 ◽

Cited By ~ 12

Author(s):

Kwang S. Kim ◽

John E. Donelson

Keyword(s):

Surface Glycoprotein ◽

Variant Surface Glycoprotein ◽

African Trypanosomes ◽

Glycoprotein Gene ◽

Expression Site

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Expression of a retroposon-like sequence upstream of the putative Trypanosoma brucei variant surface glycoprotein gene expression site promoter.

Molecular and Cellular Biology ◽

10.1128/mcb.13.11.7036 ◽

1993 ◽

Vol 13 (11) ◽

pp. 7036-7044 ◽

Cited By ~ 11

Author(s):

M J Lodes ◽

B L Smiley ◽

A W Stadnyk ◽

J L Bennett ◽

P J Myler ◽

...

Keyword(s):

Gene Expression ◽

Trypanosoma Brucei ◽

Copy Number ◽

Surface Glycoprotein ◽

Variant Surface Glycoprotein ◽

Putative Promoter ◽

Glycoprotein Gene ◽

Active Expression ◽

Expression Site ◽

Total Copy Number

We have cloned the region spanning the putative promoter from two variant surface glycoprotein gene expression sites that are at each end of chromosome M4 of Trypanosoma brucei IsTat 7. Both expression sites contain a retroposon-like sequence (ESR) pseudogene whose 3' end is approximately 30 bp upstream of the putative expression site promoter. The ESRs from both expression sites share considerable sequence homology and are related to LINE-like elements, especially the T. brucei ingi retroposon. Other ESRs are located on large, but not intermediate or mini-, chromosomes in the IsTaR 1 serodeme, and the total copy number is 10 to 20, similar to that estimated for variant surface glycoprotein expression sites. No DNA rearrangements in the vicinity of the ESR and putative expression site promoter were detected following antigenic switches in the IsTaR 1 serodeme. ESR transcripts are present in bloodstream, but not procyclic, forms. Variation in transcript size and sequence between bloodstream variant antigenic types implies that only the ESR from the active expression site is transcribed. This pattern of expression reflects that of sequences downstream of the putative expression site promoter, suggesting that the region of coordinately controlled expression extends upstream of this promoter.

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