Unravelling the hidden DNA structural/physical code provides novel insights on promoter location

Although protein recognition of DNA motifs in promoter regions has been traditionally considered as a critical regulatory element in transcription, the location of promoters, and in particular transcription start sites (TSSs), still remains a challenge. Here we perform a comprehensive analysis of pu...

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Bibliographic Details
Published in:Nucleic acids research 2013-08, Vol.41 (15), p.7220-7230
Main Authors: Durán, Elisa, Djebali, Sarah, González, Santi, Flores, Oscar, Mercader, Josep Maria, Guigó, Roderic, Torrents, David, Soler-López, Montserrat, Orozco, Modesto
Format: Article
Language:English
Subjects:
Animals
Chromatin - genetics
Computational Biology - methods
Conserved Sequence
Epigenesis, Genetic
Gene Regulation, Chromatin and Epigenetics
Genetic Code
Genoma humà
Genome, Human
Genètica
Histones - genetics
Histones - metabolism
Humans
Nucleic Acid Conformation
Promoter Regions, Genetic
Sequence Analysis, DNA
Software
Transcription, Genetic
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Summary:Although protein recognition of DNA motifs in promoter regions has been traditionally considered as a critical regulatory element in transcription, the location of promoters, and in particular transcription start sites (TSSs), still remains a challenge. Here we perform a comprehensive analysis of putative core promoter sequences relative to non-annotated predicted TSSs along the human genome, which were defined by distinct DNA physical properties implemented in our ProStar computational algorithm. A representative sampling of predicted regions was subjected to extensive experimental validation and analyses. Interestingly, the vast majority proved to be transcriptionally active despite the lack of specific sequence motifs, indicating that physical signaling is indeed able to detect promoter activity beyond conventional TSS prediction methods. Furthermore, highly active regions displayed typical chromatin features associated to promoters of housekeeping genes. Our results enable to redefine the promoter signatures and analyze the diversity, evolutionary conservation and dynamic regulation of human core promoters at large-scale. Moreover, the present study strongly supports the hypothesis of an ancient regulatory mechanism encoded by the intrinsic physical properties of the DNA that may contribute to the complexity of transcription regulation in the human genome.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gkt511