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. 1998 Mar;8(3):319-26.
doi: 10.1101/gr.8.3.319.

Identification of human gene core promoters in silico

M Q Zhang  1
Affiliations

Identification of human gene core promoters in silico

M Q Zhang. Genome Res. 1998 Mar.

Abstract

Identification of the 5'-end of human genes requires identification of functional promoter elements. In silico identification of those elements is difficult because of the hierarchical and modular nature of promoter architecture. To address this problem, I propose a new stepwise strategy based on initial localization of a functional promoter into a 1- to 2-kb (extended promoter) region from within a large genomic DNA sequence of 100 kb or larger and further localization of a transcriptional start site (TSS) into a 50- to 100-bp (corepromoter) region. Using positional dependent 5-tuple measures, a quadratic discriminant analysis (QDA) method has been implemented in a new program-CorePromoter. Our experiments indicate that when given a 1- to 2-kb extended promoter, CorePromoter will correctly localize the TSS to a 100-bp interval approximately 60% of the time. [Figure 3 can be found in its entirety as an online supplement at http://www.genome.org.]

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Figures

Figure 1
Figure 1
Core promoter organization: (UPE and DPE) Upstream and downstream promoter elements; (X) a UPE-binding TF; (CIF) a Co–Inr TF; (A,B,D,F,E,H) TFIIA, TFIIB, etc.; (TBP) the TATA box-binding protein; (TF150 and TF250) TBP-associated factors (TAFs) 150 and 250, respectively.
Figure 2
Figure 2
Top panels are LDA profiles for 10 extended EPD48 human promoter sequences. Bottom panels are QDA profiles for the same 10 sequences. The EPD entry-ID is indicated for each sequence. The vertical lines are the true TSS positions. The sequence range is (−600, +600). A peak in the profile indicates a high likelihood for a TSS.
Figure 3
Figure 3
QDA profiles (in log10 scale) for a newly constructed nonredundant human promoter database LEDB (673 sequences with 55 identical to EPD sequences) were depicted by up to the three highest peaks (see text for details). The GenBank accession no. and the TSS position are indicated at left. Each peak is also indicated by its rank number: (1) the highest peak in the whole profile, (2) the second highest, etc. The sequence range is (−600, +600), and the true TSS position is indicated by a vertical dotted line.
Figure 4
Figure 4
Similar QDA profiles to those in Fig. 3 for the 122 extended EPD promoters that were not used as the training set. (1) A strong TATA promoter.
Figure 5
Figure 5
The scatter plot of QDA scores (in log10 scale) for the peaks in (−50, +50) in Fig. 4 vs. the TATA scores (see text for detail).
Figure 6
Figure 6
Feature variables in discriminant analyses.
See this image and copyright information in PMC

References

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