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Genome organization is a major component of gene expression control in response to stress and during the cell division cycle in trypanosomes.

Kelly S, Kramer S, Schwede A, Maini PK, Gull K, Carrington M - Open Biol (2012)

Bottom Line: We show that genes encoding mRNAs that are differentially regulated during the heat-shock response are selectively positioned in polycistronic transcription units; downregulated genes are close to transcription initiation sites and upregulated genes are distant.We demonstrate that the position of a reporter gene within a transcription unit is sufficient to reproduce this effect.Furthermore, we show that the relative abundance of mRNAs at different time points in the cell division cycle is dependent on the location of the corresponding genes to transcription initiation sites.

View Article: PubMed Central - PubMed

Affiliation: Department of Plant Sciences, University of Oxford, South Parks Road, Oxford OX1 3RB, UK. steven.kelly@plants.ox.ac.uk

ABSTRACT
The trypanosome genome is characterized by RNA polymerase II-driven polycistronic transcription of protein-coding genes. Ten to hundreds of genes are co-transcribed from a single promoter; thus, selective regulation of individual genes via initiation is impossible. However, selective responses to external stimuli occur and post-transcriptional mechanisms are thought to account for all temporal gene expression patterns. We show that genes encoding mRNAs that are differentially regulated during the heat-shock response are selectively positioned in polycistronic transcription units; downregulated genes are close to transcription initiation sites and upregulated genes are distant. We demonstrate that the position of a reporter gene within a transcription unit is sufficient to reproduce this effect. Analysis of gene ontology annotations reveals that positional bias is not restricted to stress-response genes and that there is a genome-wide organization based on proximity to transcription initiation sites. Furthermore, we show that the relative abundance of mRNAs at different time points in the cell division cycle is dependent on the location of the corresponding genes to transcription initiation sites. This work provides evidence that the genome in trypanosomes is organized to facilitate co-coordinated temporal control of gene expression in the absence of selective promoters.

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(a) Plot of fold change in mRNA abundance after heat-shock against distance of corresponding gene from nearest correct orientation transcription initiation site for mRNAs that were greater than twofold differentially regulated. (b) Histogram of proportion of genes at different distances from transcription initiation sites. Black bars indicate distribution of all genes in the genome. Grey bars indicate the distribution of genes whose mRNA abundance decreases by twofold or more on heat shock. (c) Histogram of proportion of genes at different distances relative to transcription initiation sites. Black bars indicate distribution of all genes in the genome. Grey bars indicate the distribution of genes whose mRNA abundance increases by twofold or more on heat shock.
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RSOB120033F2: (a) Plot of fold change in mRNA abundance after heat-shock against distance of corresponding gene from nearest correct orientation transcription initiation site for mRNAs that were greater than twofold differentially regulated. (b) Histogram of proportion of genes at different distances from transcription initiation sites. Black bars indicate distribution of all genes in the genome. Grey bars indicate the distribution of genes whose mRNA abundance decreases by twofold or more on heat shock. (c) Histogram of proportion of genes at different distances relative to transcription initiation sites. Black bars indicate distribution of all genes in the genome. Grey bars indicate the distribution of genes whose mRNA abundance increases by twofold or more on heat shock.

Mentions: To quantify and test this observation, the fold change in abundance of individual mRNAs was plotted against the distance of the cognate genes from their transcription initiation sites (figure 2a). This revealed that there was a significant positive correlation between these values, with Spearman's rank correlation coefficient r = 0.476, the probability of this being p < 0.0001 (Pearson product–moment correlation coefficient = 0.501, p < 0.0001). To determine whether this correlation reflects a bias in the relative position of heat-shock responsive genes, the location of these genes was interrogated in the context of the underlying distribution of all genes in the genome. More than 36 per cent of the genes whose mRNA abundance decreased following heat shock occur within 20 kbp of a transcription initiation site (figure 2b); this is more than twice the value expected if downregulated genes were distributed randomly in the genome (17.8%, figure 2b). In contrast to this, genes whose mRNA abundance increased in response to heat shock are under-represented near transcription initiation sites, with only 3 per cent of responsive genes occurring in the same interval (figure 2c). Moreover, genes encoding mRNAs that increased after heat shock are over-represented at distances greater than 120 kb from the nearest transcription initiation site (figure 2c). The mean distances for each group of genes are significantly different (all p < 0.0001, determined by Monte Carlo resampling of the data). While the full complement of genes that are necessary to mediate the heat-shock response is not yet defined, the two verified heat-shock-responsive HSPs [27] are both located near the ends of transcription units: both the tandem array of 10 HSP83 genes and the HSP70 (Tb11.01.3110) gene are located at larger-than-average distances from transcription start sites. This analysis provides evidence that there is a genome-wide functional positioning of genes within transcription units that contributes to the differential temporal response of mRNAs to stress, genes proximal to the initiation sites are downregulated following heat shock and genes distant to initiation sites are upregulated.Figure 2.


Genome organization is a major component of gene expression control in response to stress and during the cell division cycle in trypanosomes.

Kelly S, Kramer S, Schwede A, Maini PK, Gull K, Carrington M - Open Biol (2012)

(a) Plot of fold change in mRNA abundance after heat-shock against distance of corresponding gene from nearest correct orientation transcription initiation site for mRNAs that were greater than twofold differentially regulated. (b) Histogram of proportion of genes at different distances from transcription initiation sites. Black bars indicate distribution of all genes in the genome. Grey bars indicate the distribution of genes whose mRNA abundance decreases by twofold or more on heat shock. (c) Histogram of proportion of genes at different distances relative to transcription initiation sites. Black bars indicate distribution of all genes in the genome. Grey bars indicate the distribution of genes whose mRNA abundance increases by twofold or more on heat shock.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376733&req=5

RSOB120033F2: (a) Plot of fold change in mRNA abundance after heat-shock against distance of corresponding gene from nearest correct orientation transcription initiation site for mRNAs that were greater than twofold differentially regulated. (b) Histogram of proportion of genes at different distances from transcription initiation sites. Black bars indicate distribution of all genes in the genome. Grey bars indicate the distribution of genes whose mRNA abundance decreases by twofold or more on heat shock. (c) Histogram of proportion of genes at different distances relative to transcription initiation sites. Black bars indicate distribution of all genes in the genome. Grey bars indicate the distribution of genes whose mRNA abundance increases by twofold or more on heat shock.
Mentions: To quantify and test this observation, the fold change in abundance of individual mRNAs was plotted against the distance of the cognate genes from their transcription initiation sites (figure 2a). This revealed that there was a significant positive correlation between these values, with Spearman's rank correlation coefficient r = 0.476, the probability of this being p < 0.0001 (Pearson product–moment correlation coefficient = 0.501, p < 0.0001). To determine whether this correlation reflects a bias in the relative position of heat-shock responsive genes, the location of these genes was interrogated in the context of the underlying distribution of all genes in the genome. More than 36 per cent of the genes whose mRNA abundance decreased following heat shock occur within 20 kbp of a transcription initiation site (figure 2b); this is more than twice the value expected if downregulated genes were distributed randomly in the genome (17.8%, figure 2b). In contrast to this, genes whose mRNA abundance increased in response to heat shock are under-represented near transcription initiation sites, with only 3 per cent of responsive genes occurring in the same interval (figure 2c). Moreover, genes encoding mRNAs that increased after heat shock are over-represented at distances greater than 120 kb from the nearest transcription initiation site (figure 2c). The mean distances for each group of genes are significantly different (all p < 0.0001, determined by Monte Carlo resampling of the data). While the full complement of genes that are necessary to mediate the heat-shock response is not yet defined, the two verified heat-shock-responsive HSPs [27] are both located near the ends of transcription units: both the tandem array of 10 HSP83 genes and the HSP70 (Tb11.01.3110) gene are located at larger-than-average distances from transcription start sites. This analysis provides evidence that there is a genome-wide functional positioning of genes within transcription units that contributes to the differential temporal response of mRNAs to stress, genes proximal to the initiation sites are downregulated following heat shock and genes distant to initiation sites are upregulated.Figure 2.

Bottom Line: We show that genes encoding mRNAs that are differentially regulated during the heat-shock response are selectively positioned in polycistronic transcription units; downregulated genes are close to transcription initiation sites and upregulated genes are distant.We demonstrate that the position of a reporter gene within a transcription unit is sufficient to reproduce this effect.Furthermore, we show that the relative abundance of mRNAs at different time points in the cell division cycle is dependent on the location of the corresponding genes to transcription initiation sites.

View Article: PubMed Central - PubMed

Affiliation: Department of Plant Sciences, University of Oxford, South Parks Road, Oxford OX1 3RB, UK. steven.kelly@plants.ox.ac.uk

ABSTRACT
The trypanosome genome is characterized by RNA polymerase II-driven polycistronic transcription of protein-coding genes. Ten to hundreds of genes are co-transcribed from a single promoter; thus, selective regulation of individual genes via initiation is impossible. However, selective responses to external stimuli occur and post-transcriptional mechanisms are thought to account for all temporal gene expression patterns. We show that genes encoding mRNAs that are differentially regulated during the heat-shock response are selectively positioned in polycistronic transcription units; downregulated genes are close to transcription initiation sites and upregulated genes are distant. We demonstrate that the position of a reporter gene within a transcription unit is sufficient to reproduce this effect. Analysis of gene ontology annotations reveals that positional bias is not restricted to stress-response genes and that there is a genome-wide organization based on proximity to transcription initiation sites. Furthermore, we show that the relative abundance of mRNAs at different time points in the cell division cycle is dependent on the location of the corresponding genes to transcription initiation sites. This work provides evidence that the genome in trypanosomes is organized to facilitate co-coordinated temporal control of gene expression in the absence of selective promoters.

Show MeSH
Related in: MedlinePlus