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Sequence features of yeast and human core promoters that are predictive of maximal promoter activity.

Lubliner S, Keren L, Segal E - Nucleic Acids Res. (2013)

Bottom Line: These features are mainly located in the region 75 bp upstream and 50 bp downstream of the main transcription start site, and their associations hold for both constitutively active promoters and promoters that are induced or repressed in specific conditions.Our results unravel several architectural features of yeast core promoters and suggest that the yeast core promoter sequence downstream of the TATA box (or of similar sequences involved in recruitment of the pre-initiation complex) is a major determinant of maximal promoter activity.We further show that human core promoters also contain features that are indicative of maximal promoter activity; thus, our results emphasize the important role of the core promoter sequence in transcriptional regulation.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel.

ABSTRACT
The core promoter is the region in which RNA polymerase II is recruited to the DNA and acts to initiate transcription, but the extent to which the core promoter sequence determines promoter activity levels is largely unknown. Here, we identified several base content and k-mer sequence features of the yeast core promoter sequence that are highly predictive of maximal promoter activity. These features are mainly located in the region 75 bp upstream and 50 bp downstream of the main transcription start site, and their associations hold for both constitutively active promoters and promoters that are induced or repressed in specific conditions. Our results unravel several architectural features of yeast core promoters and suggest that the yeast core promoter sequence downstream of the TATA box (or of similar sequences involved in recruitment of the pre-initiation complex) is a major determinant of maximal promoter activity. We further show that human core promoters also contain features that are indicative of maximal promoter activity; thus, our results emphasize the important role of the core promoter sequence in transcriptional regulation.

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5′UTR length may affect expression in constitutive genes. Cumulative distributions of 5′UTR lengths (32) for four gene subsets. 5′UTRs of constitutive–high genes tend to be shorter than those of the other three subsets (rank-sum P-values < 10−5).
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gkt256-F5: 5′UTR length may affect expression in constitutive genes. Cumulative distributions of 5′UTR lengths (32) for four gene subsets. 5′UTRs of constitutive–high genes tend to be shorter than those of the other three subsets (rank-sum P-values < 10−5).

Mentions: Robust feature 42 is the occurrence of the ‘AATG’ 4-mer within the 50 bp downstream of the main TSS, and has a positive effect. This feature may in fact represent a translation-related signal, suggesting that a short 5′UTR contributes to higher translation rates (recall that the promoter activity measures were based on YFP measurements), perhaps in relation with the ribosome scanning of the mRNA for the first AUG (34). To further assess this result, we compared 5′UTR lengths (32) of four gene subsets: constitutive–high, constitutive–low, regulated–high and regulated–low. Figure 5 shows the cumulative distributions of 5′UTR lengths for these four subsets. For constitutive–high genes alone, 5′UTRs were found to be significantly shorter than those of the other subsets (rank-sum P-values < 10−5). This suggests that 5′UTR length may indeed have an effect on expression for constitutive genes, but less so for regulated genes. Our result extends previous results (35,36) that showed that constitutive genes tend to have shorter 5′UTRs than other genes.Figure 5.


Sequence features of yeast and human core promoters that are predictive of maximal promoter activity.

Lubliner S, Keren L, Segal E - Nucleic Acids Res. (2013)

5′UTR length may affect expression in constitutive genes. Cumulative distributions of 5′UTR lengths (32) for four gene subsets. 5′UTRs of constitutive–high genes tend to be shorter than those of the other three subsets (rank-sum P-values < 10−5).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3675475&req=5

gkt256-F5: 5′UTR length may affect expression in constitutive genes. Cumulative distributions of 5′UTR lengths (32) for four gene subsets. 5′UTRs of constitutive–high genes tend to be shorter than those of the other three subsets (rank-sum P-values < 10−5).
Mentions: Robust feature 42 is the occurrence of the ‘AATG’ 4-mer within the 50 bp downstream of the main TSS, and has a positive effect. This feature may in fact represent a translation-related signal, suggesting that a short 5′UTR contributes to higher translation rates (recall that the promoter activity measures were based on YFP measurements), perhaps in relation with the ribosome scanning of the mRNA for the first AUG (34). To further assess this result, we compared 5′UTR lengths (32) of four gene subsets: constitutive–high, constitutive–low, regulated–high and regulated–low. Figure 5 shows the cumulative distributions of 5′UTR lengths for these four subsets. For constitutive–high genes alone, 5′UTRs were found to be significantly shorter than those of the other subsets (rank-sum P-values < 10−5). This suggests that 5′UTR length may indeed have an effect on expression for constitutive genes, but less so for regulated genes. Our result extends previous results (35,36) that showed that constitutive genes tend to have shorter 5′UTRs than other genes.Figure 5.

Bottom Line: These features are mainly located in the region 75 bp upstream and 50 bp downstream of the main transcription start site, and their associations hold for both constitutively active promoters and promoters that are induced or repressed in specific conditions.Our results unravel several architectural features of yeast core promoters and suggest that the yeast core promoter sequence downstream of the TATA box (or of similar sequences involved in recruitment of the pre-initiation complex) is a major determinant of maximal promoter activity.We further show that human core promoters also contain features that are indicative of maximal promoter activity; thus, our results emphasize the important role of the core promoter sequence in transcriptional regulation.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel.

ABSTRACT
The core promoter is the region in which RNA polymerase II is recruited to the DNA and acts to initiate transcription, but the extent to which the core promoter sequence determines promoter activity levels is largely unknown. Here, we identified several base content and k-mer sequence features of the yeast core promoter sequence that are highly predictive of maximal promoter activity. These features are mainly located in the region 75 bp upstream and 50 bp downstream of the main transcription start site, and their associations hold for both constitutively active promoters and promoters that are induced or repressed in specific conditions. Our results unravel several architectural features of yeast core promoters and suggest that the yeast core promoter sequence downstream of the TATA box (or of similar sequences involved in recruitment of the pre-initiation complex) is a major determinant of maximal promoter activity. We further show that human core promoters also contain features that are indicative of maximal promoter activity; thus, our results emphasize the important role of the core promoter sequence in transcriptional regulation.

Show MeSH