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Splicing factor and exon profiling across human tissues.

de la Grange P, Gratadou L, Delord M, Dutertre M, Auboeuf D - Nucleic Acids Res. (2010)

Bottom Line: It has been shown that alternative splicing is especially prevalent in brain and testis when compared to other tissues.To test whether there is a specific propensity of these tissues to generate splicing variants, we used a single source of high-density microarray data to perform both splicing factor and exon expression profiling across 11 normal human tissues.In addition to providing a unique resource on expression profiling of alternative splicing variants and splicing factors across human tissues, this study demonstrates that the higher prevalence of alternative splicing in a subset of tissues originates from the larger number of genes, including splicing factors, being expressed than in other tissues.

View Article: PubMed Central - PubMed

Affiliation: GenoSplice technology, Centre Hayem, Hôpital Saint-Louis, 1 avenue Claude Vellefaux, 75010, Paris, France. didier.auboeuf@inserm.fr

ABSTRACT
It has been shown that alternative splicing is especially prevalent in brain and testis when compared to other tissues. To test whether there is a specific propensity of these tissues to generate splicing variants, we used a single source of high-density microarray data to perform both splicing factor and exon expression profiling across 11 normal human tissues. Paired comparisons between tissues and an original exon-based statistical group analysis demonstrated after extensive RT-PCR validation that the cerebellum, testis, and spleen had the largest proportion of differentially expressed alternative exons. Variations at the exon level correlated with a larger number of splicing factors being expressed at a high level in the cerebellum, testis and spleen than in other tissues. However, this splicing factor expression profile was similar to a more global gene expression pattern as a larger number of genes had a high expression level in the cerebellum, testis and spleen. In addition to providing a unique resource on expression profiling of alternative splicing variants and splicing factors across human tissues, this study demonstrates that the higher prevalence of alternative splicing in a subset of tissues originates from the larger number of genes, including splicing factors, being expressed than in other tissues.

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Profile of gene expression across 11 tissues. (A) Number of transcription factors being up- or down-expressed in each tissue compared to their average expression level in the 11 tissues. The mean of the gene signal in the 11 tissues was calculated for each transcription factor. The distance between the gene signal in a given tissue and the corresponding mean in the 11 tissues was calculated. The number of transcription factors with a gene expression level above or below the gene expression average in the 11 tissues was calculated. (B) Percentage of selected probesets expressed above DABG in each tissue. (C) Number of genes expressed above DABG in each tissue. (D) Statistical group analysis of gene expression levels. The tissue ranking using gene expression level (gene signal) values in parallel to those of alternative exons (compared with Figures 2B); that is, the same types of samples with the largest number of differentially expressed exon (spleen, cerebellum and testes, see Figure 2B) were among those with the most differentially expressed genes. (E) Percentage in each tissue of genes that were significantly expressed in 11 tissues and that contained differentially expressed exons in paired comparisons. The proportion of genes with differentially expressed exons in each tissue was calculated among 524 genes (corresponding to 100%) that were significantly expressed in the 11 tissues and that were predicted to contain differentially expressed alternative exons in all paired comparisons. (F) Percentage in each tissue of genes that were significantly expressed in 11 tissues and that contained differentially expressed exons in group comparisons. The proportion of genes with differentially expressed exons in each tissue was calculated among 196 genes (corresponding to 100%) that were significantly expressed in the 11 tissues and that were predicted to contain differentially expressed alternative exons in all group comparisons.
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Figure 6: Profile of gene expression across 11 tissues. (A) Number of transcription factors being up- or down-expressed in each tissue compared to their average expression level in the 11 tissues. The mean of the gene signal in the 11 tissues was calculated for each transcription factor. The distance between the gene signal in a given tissue and the corresponding mean in the 11 tissues was calculated. The number of transcription factors with a gene expression level above or below the gene expression average in the 11 tissues was calculated. (B) Percentage of selected probesets expressed above DABG in each tissue. (C) Number of genes expressed above DABG in each tissue. (D) Statistical group analysis of gene expression levels. The tissue ranking using gene expression level (gene signal) values in parallel to those of alternative exons (compared with Figures 2B); that is, the same types of samples with the largest number of differentially expressed exon (spleen, cerebellum and testes, see Figure 2B) were among those with the most differentially expressed genes. (E) Percentage in each tissue of genes that were significantly expressed in 11 tissues and that contained differentially expressed exons in paired comparisons. The proportion of genes with differentially expressed exons in each tissue was calculated among 524 genes (corresponding to 100%) that were significantly expressed in the 11 tissues and that were predicted to contain differentially expressed alternative exons in all paired comparisons. (F) Percentage in each tissue of genes that were significantly expressed in 11 tissues and that contained differentially expressed exons in group comparisons. The proportion of genes with differentially expressed exons in each tissue was calculated among 196 genes (corresponding to 100%) that were significantly expressed in the 11 tissues and that were predicted to contain differentially expressed alternative exons in all group comparisons.

Mentions: To test whether there was a propensity of cerebellum, testis and spleen to generate transcripts with a different exon content from that of other tissues (Figure 5A), we investigated whether a high expression level of splicing factors was a specific feature of these tissues. First, similar results were obtained by performing transcription factor gene expression profiling, as a larger proportion of transcription factors were more expressed in the cerebellum, testis and spleen than in the other tissues and a smaller proportion of transcription factors were less expressed in the cerebellum, testis and spleen than in the other tissues, as observed for splicing factors (comparing Figures 5C and 6A). Second, we observed that a larger proportion of probesets were above the DABG in the cerebellum, testis and spleen than in the other tissues (Figure 6B). Third, there were almost twice more genes expressed in the cerebellum, testis, and spleen than in the other tissues (Figure 6C). Finally, a statistical group analysis based on gene expression level (gene signal) revealed that the tissues expressing a larger proportion of differentially expressed genes were those expressing a larger proportion of differentially expressed exons (comparing Figures 2B and 6D). Therefore, these analyses revealed that the larger number of splicing factors being highly expressed in the cerebellum, testis and spleen (Figure 5C and D) is likely to be part of a more global profile of gene expression (Figure 6). This was strengthened by the observation of a similar ranking by analyzing ASEs, AFE and ALEs (Figure 5A). Altogether, the apparent propensity of cerebellum, testis and spleen to express more alternative transcripts than other tissues is likely to originate from their ability to express more genes.Figure 6.


Splicing factor and exon profiling across human tissues.

de la Grange P, Gratadou L, Delord M, Dutertre M, Auboeuf D - Nucleic Acids Res. (2010)

Profile of gene expression across 11 tissues. (A) Number of transcription factors being up- or down-expressed in each tissue compared to their average expression level in the 11 tissues. The mean of the gene signal in the 11 tissues was calculated for each transcription factor. The distance between the gene signal in a given tissue and the corresponding mean in the 11 tissues was calculated. The number of transcription factors with a gene expression level above or below the gene expression average in the 11 tissues was calculated. (B) Percentage of selected probesets expressed above DABG in each tissue. (C) Number of genes expressed above DABG in each tissue. (D) Statistical group analysis of gene expression levels. The tissue ranking using gene expression level (gene signal) values in parallel to those of alternative exons (compared with Figures 2B); that is, the same types of samples with the largest number of differentially expressed exon (spleen, cerebellum and testes, see Figure 2B) were among those with the most differentially expressed genes. (E) Percentage in each tissue of genes that were significantly expressed in 11 tissues and that contained differentially expressed exons in paired comparisons. The proportion of genes with differentially expressed exons in each tissue was calculated among 524 genes (corresponding to 100%) that were significantly expressed in the 11 tissues and that were predicted to contain differentially expressed alternative exons in all paired comparisons. (F) Percentage in each tissue of genes that were significantly expressed in 11 tissues and that contained differentially expressed exons in group comparisons. The proportion of genes with differentially expressed exons in each tissue was calculated among 196 genes (corresponding to 100%) that were significantly expressed in the 11 tissues and that were predicted to contain differentially expressed alternative exons in all group comparisons.
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Figure 6: Profile of gene expression across 11 tissues. (A) Number of transcription factors being up- or down-expressed in each tissue compared to their average expression level in the 11 tissues. The mean of the gene signal in the 11 tissues was calculated for each transcription factor. The distance between the gene signal in a given tissue and the corresponding mean in the 11 tissues was calculated. The number of transcription factors with a gene expression level above or below the gene expression average in the 11 tissues was calculated. (B) Percentage of selected probesets expressed above DABG in each tissue. (C) Number of genes expressed above DABG in each tissue. (D) Statistical group analysis of gene expression levels. The tissue ranking using gene expression level (gene signal) values in parallel to those of alternative exons (compared with Figures 2B); that is, the same types of samples with the largest number of differentially expressed exon (spleen, cerebellum and testes, see Figure 2B) were among those with the most differentially expressed genes. (E) Percentage in each tissue of genes that were significantly expressed in 11 tissues and that contained differentially expressed exons in paired comparisons. The proportion of genes with differentially expressed exons in each tissue was calculated among 524 genes (corresponding to 100%) that were significantly expressed in the 11 tissues and that were predicted to contain differentially expressed alternative exons in all paired comparisons. (F) Percentage in each tissue of genes that were significantly expressed in 11 tissues and that contained differentially expressed exons in group comparisons. The proportion of genes with differentially expressed exons in each tissue was calculated among 196 genes (corresponding to 100%) that were significantly expressed in the 11 tissues and that were predicted to contain differentially expressed alternative exons in all group comparisons.
Mentions: To test whether there was a propensity of cerebellum, testis and spleen to generate transcripts with a different exon content from that of other tissues (Figure 5A), we investigated whether a high expression level of splicing factors was a specific feature of these tissues. First, similar results were obtained by performing transcription factor gene expression profiling, as a larger proportion of transcription factors were more expressed in the cerebellum, testis and spleen than in the other tissues and a smaller proportion of transcription factors were less expressed in the cerebellum, testis and spleen than in the other tissues, as observed for splicing factors (comparing Figures 5C and 6A). Second, we observed that a larger proportion of probesets were above the DABG in the cerebellum, testis and spleen than in the other tissues (Figure 6B). Third, there were almost twice more genes expressed in the cerebellum, testis, and spleen than in the other tissues (Figure 6C). Finally, a statistical group analysis based on gene expression level (gene signal) revealed that the tissues expressing a larger proportion of differentially expressed genes were those expressing a larger proportion of differentially expressed exons (comparing Figures 2B and 6D). Therefore, these analyses revealed that the larger number of splicing factors being highly expressed in the cerebellum, testis and spleen (Figure 5C and D) is likely to be part of a more global profile of gene expression (Figure 6). This was strengthened by the observation of a similar ranking by analyzing ASEs, AFE and ALEs (Figure 5A). Altogether, the apparent propensity of cerebellum, testis and spleen to express more alternative transcripts than other tissues is likely to originate from their ability to express more genes.Figure 6.

Bottom Line: It has been shown that alternative splicing is especially prevalent in brain and testis when compared to other tissues.To test whether there is a specific propensity of these tissues to generate splicing variants, we used a single source of high-density microarray data to perform both splicing factor and exon expression profiling across 11 normal human tissues.In addition to providing a unique resource on expression profiling of alternative splicing variants and splicing factors across human tissues, this study demonstrates that the higher prevalence of alternative splicing in a subset of tissues originates from the larger number of genes, including splicing factors, being expressed than in other tissues.

View Article: PubMed Central - PubMed

Affiliation: GenoSplice technology, Centre Hayem, Hôpital Saint-Louis, 1 avenue Claude Vellefaux, 75010, Paris, France. didier.auboeuf@inserm.fr

ABSTRACT
It has been shown that alternative splicing is especially prevalent in brain and testis when compared to other tissues. To test whether there is a specific propensity of these tissues to generate splicing variants, we used a single source of high-density microarray data to perform both splicing factor and exon expression profiling across 11 normal human tissues. Paired comparisons between tissues and an original exon-based statistical group analysis demonstrated after extensive RT-PCR validation that the cerebellum, testis, and spleen had the largest proportion of differentially expressed alternative exons. Variations at the exon level correlated with a larger number of splicing factors being expressed at a high level in the cerebellum, testis and spleen than in other tissues. However, this splicing factor expression profile was similar to a more global gene expression pattern as a larger number of genes had a high expression level in the cerebellum, testis and spleen. In addition to providing a unique resource on expression profiling of alternative splicing variants and splicing factors across human tissues, this study demonstrates that the higher prevalence of alternative splicing in a subset of tissues originates from the larger number of genes, including splicing factors, being expressed than in other tissues.

Show MeSH
Related in: MedlinePlus