Cooperative silencing elements in var genes

Deitsch, Kirk W.; Calderwood, Michael S.; Wellems, Thomas E.

doi:10.1038/35091146

Cited by 199 publications

(174 citation statements)

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“…These sequences are not found in blood stage promoters such as hrp3, msp1, var7b and knob-associated histidine rich protein (kahrp), suggesting that they are not involved in regulation of stage specificity in these promoters. Also, it has been reported that intronic regulatory elements regulate allelic expression in centromeric var7b genes [15,36]. Similarly, hrp3 5' end sequence contains an intron located 13 bp upstream of the ATG initiation codon [27].…”

Section: Discussionmentioning

confidence: 99%

“…For example, early studies of the regulation of glycophorin binding protein 130 (gbp130) showed that the loss of trophozoite stage specificity was correlated with rearrangement of the chromatin structure on the plasmid copy [12]. In contrast, P. falciparum stage specific promoters such as histidine-rich protein-3 (hrp3) [25], PfEMP1 (var) [15] and P. berghei apical membrane antigen-1 promoter (Pbama1) [32] used to drive reporter gene expression on plasmids, maintained a strict developmental regulation despite the change in location. Together, these results indicate that regulatory mechanisms in the parasite might not be entirely dependent on chromosomal location.…”

Section: Location Of the Hrp3 Promoter On An Episome Did Not Affect Tmentioning

confidence: 99%

“…Kpn I-Dra III-digested pHRPCAT was incubated with exonuclease III (exo III) at predetermined times to obtain specific-sized promoters of 1.1-kb and 0.6-kb. The firefly luciferase (FFL) gene was amplified by PCR from the pVLH plasmid [15] using oligonucleotides 5'-GACATGCATGAAGACGCCAAAAACATAAAG-3' and 5'-GACAAGCTTGCTTACAATTTGGACTTTCCG-3', (boldfaced nucleotides represent Nsi I and Hind III restriction sites, respectively). The FFL was then used to replace the CAT gene in exoIII-digested pHRPCAT to generate pH1.7FL, pH1.1FL and pH0.6FL.…”

Section: Plasmid Constructsmentioning

confidence: 99%

“…While transcriptome and proteome analyses indicate that some genes are regulated post-transcriptionally [8,9], other genes are regulated at the level of transcription. For example, analyses of 5' end upstream regions of the asexual and sexual stages have been shown by transfection studies that they function as promoters by supporting reporter gene expression [10][11][12][13][14][15][16]. Moreover, functional and bioinformatic studies of sexual and asexual Plasmodium promoters have uncovered putative cis-acting regulatory elements possibly involved in gene regulation [17][18][19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

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An enhancer-like region regulates hrp3 promoter stage-specific gene expression in the human malaria parasite Plasmodium falciparum

López-Estraño

Gopalakrishnan

Semblat

et al. 2007

Biochimica et Biophysica Acta (BBA) - Gene Structure and Expres

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The asexual blood stage of Plasmodium falciparum is comprised of morphologically distinct ring, trophozoite and schizont stages. Each of these developmental stages possesses a distinct pattern of gene expression. Regulation of P. falciparum gene expression is thought to occur, at least in part, at the promoter level. Previously, we have found that although the RNA of the P. falciparum hrp3 gene is only seen in ring-stage parasites, deletion of a specific sequensce in the 5' end of the promoter region decreased ring-stage expression of hrp3 and enabled detection of its transcripts in trophozoitestage parasites. In order to investigate this stage specific regulation of gene expression, we employed a series of nested deletions of the 1.7-kb hrp3 promoter. Firefly luciferase gene was used as a reporter to evaluate the role of promoter sequences in gene regulation. Using this approach, we identified a ring-stage specific regulatory region on the hrp3 promoter located between -1.7-kb and -1.1-kb from the ATG initiation codon. Small 100-150 bp truncations on this enhancer-like region failed to uncover discrete regulatory sequences, suggesting the multipartite nature of this element. The data presented in this study demonstrates that stage specific promoter activity of the hrp3 gene in P. falciparum blood stage parasites is supported, at least in-part, by a small promoter region that can function in the absence of a larger chromosomal context.

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Section: Discussionmentioning

confidence: 99%

Section: Location Of the Hrp3 Promoter On An Episome Did Not Affect Tmentioning

confidence: 99%

Section: Plasmid Constructsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

An enhancer-like region regulates hrp3 promoter stage-specific gene expression in the human malaria parasite Plasmodium falciparum

López-Estraño

Gopalakrishnan

Semblat

et al. 2007

Biochimica et Biophysica Acta (BBA) - Gene Structure and Expres

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“…It is not clear whether the var intron participates in regulating var mutually exclusive expression (46,47). Yet, the intron sequences apparently do harbor an insulator activity that antagonizes spreading of chromatin activation into neighboring loci (48).…”

Section: Cis-regulatory Elements That Control Var Expressionmentioning

confidence: 99%

Variability and Exclusion in Host and Parasite: Epigenetic Regulation of Ig and var Expression

Fraenkel

Bergman

2006

The Journal of Immunology

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The immune system generates highly diverse AgRs of different specificities from a pool of designated genomic loci, each containing large arrays of genes. Ultimately, each B or T cell expresses a receptor of a single type on its surface. Immune evasion by the malaria parasite Plasmodium falciparum is mediated by the mutually exclusive expression of a single member of the var family of genes, which encodes variant surface Ags. In this review, we discuss the similarities as well as the unique characteristics of the epigenetic mechanisms involved in the establishment of mutually exclusive expression in the immune and parasite systems.

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Evolution of Antigenic Variation

Frank

2006

Encyclopedia of Infectious Diseases

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processes that shape genetic variability and evolutionary change.The causes of variability and change provide the basis for understanding why simple vaccines work well against some viruses, whereas complex vaccine strategies achieve only limited success against other viruses.The battle between host and parasite often comes down to the rates at which attacker and defender molecules bind or evade each other. The biochemical details of binding and recognition set the rules of engagement that shape the pace, scale, and pattern of diversity and the nature of evolutionary change [45].The first section of this chapter lists the different ways in which parasites can gain by varying their antigenic molecules. The parasites may, for example, extend their time of infection within a particular host by changing their antigenic molecules to evade the specific recognition built up by the host immune system. Or the parasites may vary to attack hosts that had been exposed previously and had built up specific recognition against prior antigenic molecules.The second section focuses on the nature of binding and recognition between host and parasite molecules. I summarize the different ways in which parasites generate new variants in order to escape molecular recognition.The third section builds up the individual molecular interactions into the dynamics of a single infection within a host. The parasites spread in the host, triggering immune attack against dominant antigens.The battle within the host develops through changes in population numbers -the numbers of parasites with particular antigens and the numbers of immune cells that specifically bind to particular antigens.The fourth and fifth sections discuss how the successes and failures of different parasite antigens within each host determine the rise and fall of parasite variants over space and time. The distribution of parasite variants sets the immune memory profiles of different hosts, which in turn 225

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Cooperative silencing elements in var genes

Cited by 199 publications

References 10 publications

An enhancer-like region regulates hrp3 promoter stage-specific gene expression in the human malaria parasite Plasmodium falciparum

An enhancer-like region regulates hrp3 promoter stage-specific gene expression in the human malaria parasite Plasmodium falciparum

Variability and Exclusion in Host and Parasite: Epigenetic Regulation of Ig and var Expression

Evolution of Antigenic Variation

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