Trypanosoma brucei: constitutive activity of the VSG and procyclin gene promoters.

Pays, Étienne; Coquelet, H; Tebabi, Patricia; Pays, Annette; Jefferies, David; Steinert, Maurice; Koenig, Erik; Williams, Richard O.; Roditi, Isabel

doi:10.1002/j.1460-2075.1990.tb07512.x

Cited by 140 publications

(151 citation statements)

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“…The control of VSG gene expression during the parasite life cycle has been more extensively investigated using nuclear run-on assays. Several groups have shown that, although VSG mRNAs are not detected in procyclic forms, transcription initiation does occur at a low level from many, if not all, ES promoters (27)(28)(29). This is consistent with the observation of CAT or luciferase expression under the control of VSG gene promoters cloned in episomal vectors in transiently transfected procyclic parasites (29,30).…”

Section: Smr Teixeirasupporting

confidence: 71%

“…Several groups have shown that, although VSG mRNAs are not detected in procyclic forms, transcription initiation does occur at a low level from many, if not all, ES promoters (27)(28)(29). This is consistent with the observation of CAT or luciferase expression under the control of VSG gene promoters cloned in episomal vectors in transiently transfected procyclic parasites (29,30). However, when VSG promoters were further analyzed within their chromosomal context, instead of plasmid vectors, it was found that the transcription elongation step is subjected to stage-specific regulation, i.e., the active VSG gene is fully transcribed in bloodstream parasites but most transcriptional activity stops within 1 kb of the VSG promoter in procyclics (27)(28)(29).…”

Section: Smr Teixeiramentioning

confidence: 99%

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Control of gene expression in Trypanosomatidae

Teixeira

1998

Braz J Med Biol Res

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The study of mechanisms which control gene expression in trypanosomatids has developed at an increasing rate since 1989 when the first successful DNA transfection experiments were reported. Using primarily Trypanosoma brucei as a model, several groups have begun to elucidate the basic control mechanisms and to define the cellular factors involved in mRNA transcription, processing and translation in these parasites. This review focuses on the most recent studies regarding a subset of genes that are expressed differentially during the life cycle of three groups of parasites. In addition to T. brucei, I will address studies on gene regulation in a few species of Leishmania and the results obtained by a much more limited group of laboratories studying gene expression in Trypanosoma cruzi. It is becoming evident that the regulatory strategies chosen by different species of trypanosomatids are not similar, and that for these very successful parasites it is probably advantageous to employ multiple mechanisms simultaneously. In addition, with the increasing numbers of parasite genes that have now been submitted to molecular dissection, it is also becoming evident that, among the various strategies for gene expression control, there is a predominance of regulatory pathways acting at the post-transcriptional level.

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Section: Smr Teixeirasupporting

confidence: 71%

Section: Smr Teixeiramentioning

confidence: 99%

Control of gene expression in Trypanosomatidae

Teixeira

1998

Braz J Med Biol Res

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“…This conclusion is also true in procyclic forms, where the ES promoters are normally not active (38). The very simple structure and ribosomal nature of the ES promoters (39,40) is in keeping with the absence of regulatory sequences. In support of this notion, promoters from active or inactive ESs share the same sensitivity to DNase (24), and antigenic variation still occurs properly if the promoter of the active ES is replaced by the ribosomal promoter (41,42).…”

Section: Discussionmentioning

confidence: 76%

Transcription is initiated on silent variant surface glycoprotein expression sites despite monoallelic expression in Trypanosoma brucei

Kassem

Pays

Vanhamme

2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance African trypanosomes are a major plague in sub-Saharan Africa. They cause sleeping sickness in humans and nagana in cattle, preventing extensive cattle raising. They escape the immune system of their host through frequent changes in their major surface antigen, the variant surface glycoprotein (VSG). The control of VSG expression is poorly understood, and the level at which it takes place has been a matter of debate for the last 25 y. A better understanding of the mechanism by which it works would facilitate the identification of the proteins involved and would provide putative targets for drug design. We report data indicating an unusual control level, namely after transcription initiation, suggesting transcription elongation or RNA processing as a control step.

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“…Firstly, THT1 and THT2 RNAs (17,32,39,43). Northern blot analysis using THT1-and THT2-specific probes detected a 5-kb mRNA corresponding to a doublet of THT precursor mRNA probably derived from polycistronic transcription (data not shown).…”

Section: Discussionmentioning

confidence: 94%

Differential regulation of two distinct families of glucose transporter genes in Trypanosoma brucei.

Bringaud¹,

Baltz²

1993

Mol. Cell. Biol.

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A tandemly arranged multigene family encoding putative hexose transporters in Trypanosoma brucei has been characterized. It is composed of two 80%Yo homologous groups of genes called THT1 (six copies) and THT2 (five copies). When Xenopus oocytes are microinjected with in vitro-transcribed RNA from a THT1 gene, they express a glucose transporter with properties similar to those of the trypanosome bloodstream-form protein(s). This THT1-encoded transport system for glucose differs from the human erythrocyte-type glucose transporter by its moderate sensitivity to cytochalasin B and its capacity to transport D-fructose. These properties suggest that the trypanosomal transporter may be a good target for antitrypanosomal drugs. mRNA analysis revealed that expression of these genes was life cycle stage dependent. Bloodstream forms express 40-fold more THT1 than THT2. In contrast, procyclic trypanosomes express no detectable THT1 but demonstrate glucosedependent expression of THT2.Glucose is the major source of energy for most protozoan parasites. The uptake of this sugar across the plasma membrane is a process of fundamental importance. The wellcharacterized glucose transport systems of members from the genera Trypanosoma (14,16,18,36,38), Leishmania (46,47), and Plasmodium (37) are closely related, as judged by their substrate specificity and drug sensitivity. They act as either facilitative transporters (18,38) (14,16,36,38). Procyclic culture forms, homologous to the insect midgut stage, can thrive in the absence of glucose, preferring amino acids (mainly proline) as an energy source. Nevertheless, procyclic forms do express a glucose transport system which differs from that found in the bloodstream forms (31,38).In a previous report, we described the cloning and analysis of a developmentally regulated T. brucei gene coding for a putative hexose transporter called THT (for trypanosome hexose transporter) (9). Here we report the characterization of a multigene family encoding two highly related proteins, THT1 and THT2. The genes are all located in a single cluster containing six adjacent copies of the THT1 genes and five copies of the THT2 genes. Expression of these genes during the parasite life cycle is discussed; the hexose transporter * Corresponding author. function of the THT1 gene has been determined by expression in Xenopus oocytes. MATERIALS AND METHODSTrypanosomes. The bloodstream forms of T. brucei brucei EATRO-164 (kindly provided by R. Brun) were obtained from infected rats as described previously (26). Procyclic forms of T. brucei brucei Stib-247 (kindly provided by R. Brun) were cultured at 26°C in a semidefined medium containing 10% fetal calf serum dialyzed by ultrafiltration (Sigma F3260 filter) or undialyzed serum, 3.5 mg of hemin per ml, and 0.5 g of L-proline per liter, with or without 1 g of glucose per liter (3).Construction and screening of genomic libraries. For cloning of THTg.A, total DNA of EATRO-164 was fully digested by EcoRI, and 8-to 25-kb fragments purified by fast protein liquid chrom...

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Trypanosoma brucei: constitutive activity of the VSG and procyclin gene promoters.

Cited by 140 publications

References 38 publications

Control of gene expression in Trypanosomatidae

Control of gene expression in Trypanosomatidae

Transcription is initiated on silent variant surface glycoprotein expression sites despite monoallelic expression in Trypanosoma brucei

Differential regulation of two distinct families of glucose transporter genes in Trypanosoma brucei.

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