NDLI: Assessment of clusters of transcription factor binding sites in relationship to human promoter, CpG islands and gene expression

Content Provider	Springer Nature : BioMed Central
Author	Murakami, Katsuhiko Kojima, Toshio Sakaki, Yoshiyuki
Abstract	Gene expression is regulated mainly by transcription factors (TFs) that interact with regulatory cis-elements on DNA sequences. To identify functional regulatory elements, computer searching can predict TF binding sites (TFBS) using position weight matrices (PWMs) that represent positional base frequencies of collected experimentally determined TFBS. A disadvantage of this approach is the large output of results for genomic DNA. One strategy to identify genuine TFBS is to utilize local concentrations of predicted TFBS. It is unclear whether there is a general tendency for TFBS to cluster at promoter regions, although this is the case for certain TFBS. Also unclear is the identification of TFs that have TFBS concentrated in promoters and to what level this occurs. This study hopes to answer some of these questions. We developed the cluster score measure to evaluate the correlation between predicted TFBS clusters and promoter sequences for each PWM. Non-promoter sequences were used as a control. Using the cluster score, we identified a PWM group called PWM-PCP, in which TFBS clusters positively correlate with promoters, and another PWM group called PWM-NCP, in which TFBS clusters negatively correlate with promoters. The PWM-PCP group comprises 47% of the 199 vertebrate PWMs, while the PWM-NCP group occupied 11 percent. After reducing the effect of CpG islands (CGI) against the clusters using partial correlation coefficients among three properties (promoter, CGI and predicted TFBS cluster), we identified two PWM groups including those strongly correlated with CGI and those not correlated with CGI. Not all PWMs predict TFBS correlated with human promoter sequences. Two main PWM groups were identified: (1) those that show TFBS clustered in promoters associated with CGI, and (2) those that show TFBS clustered in promoters independent of CGI. Assessment of PWM matches will allow more positive interpretation of TFBS in regulatory regions.
Related Links	https://bmcgenomics.biomedcentral.com/counter/pdf/10.1186/1471-2164-5-16.pdf
Ending Page	17
Page Count	17
Starting Page	1
File Format	HTM / HTML
ISSN	14712164
DOI	10.1186/1471-2164-5-16
Journal	BMC Genomics
Issue Number	1
Volume Number	5
Language	English
Publisher	BioMed Central
Publisher Date	2004-02-23
Access Restriction	Open
Subject Keyword	Life Sciences Microarrays Proteomics Animal Genetics and Genomics Microbial Genetics and Genomics Plant Genetics and Genomics promoter tissue-specific gene expression position weight matrix regulatory motif
Content Type	Text
Resource Type	Article
Subject	Biotechnology Genetics
Journal Impact Factor	3.5/2023
5-Year Journal Impact Factor	4.1/2023

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