Genome-wide analysis of core promoter elements from conserved human and mouse orthologous pairs

BMC Bioinformatics
Victor X JinRamana V Davuluri

Abstract

The canonical core promoter elements consist of the TATA box, initiator (Inr), downstream core promoter element (DPE), TFIIB recognition element (BRE) and the newly-discovered motif 10 element (MTE). The motifs for these core promoter elements are highly degenerate, which tends to lead to a high false discovery rate when attempting to detect them in promoter sequences. In this study, we have performed the first analysis of these core promoter elements in orthologous mouse and human promoters with experimentally-supported transcription start sites. We have identified these various elements using a combination of positional weight matrices (PWMs) and the degree of conservation of orthologous mouse and human sequences--a procedure that significantly reduces the false positive rate of motif discovery. Our analysis of 9,010 orthologous mouse-human promoter pairs revealed two combinations of three-way synergistic effects, TATA-Inr-MTE and BRE-Inr-MTE. The former has previously been putatively identified in human, but the latter represents a novel synergistic relationship. Our results demonstrate that DNA sequence conservation can greatly improve the identification of functional core promoter elements in the human genome. The data als...Continue Reading

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Software Mentioned

MTE
TRANSFAC
TRANFAC
ClustalW
MATCH
DragonGSF
Inr
OMGProm
BRE
DPE

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