Limits...
An algorithm for identifying novel targets of transcription factor families: application to hypoxia-inducible factor 1 targets.

Jiang Y, Cukic B, Adjeroh DA, Skinner HD, Lin J, Shen QJ, Jiang BH - Cancer Inform (2009)

Bottom Line: Efficient and effective analysis of the growing genomic databases requires the development of adequate computational tools.We further studied one of the potential targets, COX-2, in the biological lab; and showed that it was a biologically relevant HIF-1 target.These results demonstrate that our methodology is an effective computational approach for identifying novel HIF-1 targets.

View Article: PubMed Central - PubMed

Affiliation: Lane Department of Computer Science and Electrical Engineering, West Virginia University, Morgantown, WV 26506, USA. yue@csee.wvu.edu

ABSTRACT
Efficient and effective analysis of the growing genomic databases requires the development of adequate computational tools. We introduce a fast method based on the suffix tree data structure for predicting novel targets of hypoxia-inducible factor 1 (HIF-1) from huge genome databases. The suffix tree data structure has two powerful applications here: one is to extract unknown patterns from multiple strings/sequences in linear time; the other is to search multiple strings/sequences using multiple patterns in linear time. Using 15 known HIF-1 target gene sequences as a training set, we extracted 105 common patterns that all occur in the 15 training genes using suffix trees. Using these 105 common patterns along with known subsequences surrounding HIF-1 binding sites from the literature, the algorithm searches a genome database that contains 2,078,786 DNA sequences. It reported 258 potentially novel HIF-1 targets including 25 known HIF-1 targets. Based on microarray studies from the literature, 17 putative genes were confirmed to be upregulated by HIF-1 or hypoxia inside these 258 genes. We further studied one of the potential targets, COX-2, in the biological lab; and showed that it was a biologically relevant HIF-1 target. These results demonstrate that our methodology is an effective computational approach for identifying novel HIF-1 targets.

No MeSH data available.


Related in: MedlinePlus

The regulation of a typical HIF-1 target gene. A HIF-1 target gene codes for a specific protein. The promoter is located immediately upstream of the coding sequence for the protein for regulating the gene expression. The enhancer is located upstream of the promoter with different lengths of spacing and with HIF-1 binding site. HIF-1 consists of HIF-1α and HIF-1β subunits. HIF-1α and HIF-1β can dimerize, and bind to the enhancer region to increase its promoter activity. HIF-1 commonly has the binding site “RCGTG” in the enhancer region.41,42,44
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC2664698&req=5

f3-cin-07-75: The regulation of a typical HIF-1 target gene. A HIF-1 target gene codes for a specific protein. The promoter is located immediately upstream of the coding sequence for the protein for regulating the gene expression. The enhancer is located upstream of the promoter with different lengths of spacing and with HIF-1 binding site. HIF-1 consists of HIF-1α and HIF-1β subunits. HIF-1α and HIF-1β can dimerize, and bind to the enhancer region to increase its promoter activity. HIF-1 commonly has the binding site “RCGTG” in the enhancer region.41,42,44

Mentions: A typical schematic diagram of a target gene activated by HIF-1 is shown in Figure 3. It is known that HIF-1 has the consensus binding site “RCGTG” (R stands for any of the four nucleotides: A, C, G, and T) at its target genes.41–44 All the known HIF-1 binding sites are at the 5′ region upstream of the promoter sequence, that is, in 5′ enhancer region, except erythropoietin (EPO) which contains HIF-1 binding site in the 3′ enhancer region. From the information provided by the annotation databases in GenBank, it is quite difficult to obtain the stop site of gene coding sequence. Therefore, in the positional analysis, we only select the potential HIF-1 candidate targets that contain HIF-1 binding sites in the 5′ region upstream of the promoter.


An algorithm for identifying novel targets of transcription factor families: application to hypoxia-inducible factor 1 targets.

Jiang Y, Cukic B, Adjeroh DA, Skinner HD, Lin J, Shen QJ, Jiang BH - Cancer Inform (2009)

The regulation of a typical HIF-1 target gene. A HIF-1 target gene codes for a specific protein. The promoter is located immediately upstream of the coding sequence for the protein for regulating the gene expression. The enhancer is located upstream of the promoter with different lengths of spacing and with HIF-1 binding site. HIF-1 consists of HIF-1α and HIF-1β subunits. HIF-1α and HIF-1β can dimerize, and bind to the enhancer region to increase its promoter activity. HIF-1 commonly has the binding site “RCGTG” in the enhancer region.41,42,44
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2664698&req=5

f3-cin-07-75: The regulation of a typical HIF-1 target gene. A HIF-1 target gene codes for a specific protein. The promoter is located immediately upstream of the coding sequence for the protein for regulating the gene expression. The enhancer is located upstream of the promoter with different lengths of spacing and with HIF-1 binding site. HIF-1 consists of HIF-1α and HIF-1β subunits. HIF-1α and HIF-1β can dimerize, and bind to the enhancer region to increase its promoter activity. HIF-1 commonly has the binding site “RCGTG” in the enhancer region.41,42,44
Mentions: A typical schematic diagram of a target gene activated by HIF-1 is shown in Figure 3. It is known that HIF-1 has the consensus binding site “RCGTG” (R stands for any of the four nucleotides: A, C, G, and T) at its target genes.41–44 All the known HIF-1 binding sites are at the 5′ region upstream of the promoter sequence, that is, in 5′ enhancer region, except erythropoietin (EPO) which contains HIF-1 binding site in the 3′ enhancer region. From the information provided by the annotation databases in GenBank, it is quite difficult to obtain the stop site of gene coding sequence. Therefore, in the positional analysis, we only select the potential HIF-1 candidate targets that contain HIF-1 binding sites in the 5′ region upstream of the promoter.

Bottom Line: Efficient and effective analysis of the growing genomic databases requires the development of adequate computational tools.We further studied one of the potential targets, COX-2, in the biological lab; and showed that it was a biologically relevant HIF-1 target.These results demonstrate that our methodology is an effective computational approach for identifying novel HIF-1 targets.

View Article: PubMed Central - PubMed

Affiliation: Lane Department of Computer Science and Electrical Engineering, West Virginia University, Morgantown, WV 26506, USA. yue@csee.wvu.edu

ABSTRACT
Efficient and effective analysis of the growing genomic databases requires the development of adequate computational tools. We introduce a fast method based on the suffix tree data structure for predicting novel targets of hypoxia-inducible factor 1 (HIF-1) from huge genome databases. The suffix tree data structure has two powerful applications here: one is to extract unknown patterns from multiple strings/sequences in linear time; the other is to search multiple strings/sequences using multiple patterns in linear time. Using 15 known HIF-1 target gene sequences as a training set, we extracted 105 common patterns that all occur in the 15 training genes using suffix trees. Using these 105 common patterns along with known subsequences surrounding HIF-1 binding sites from the literature, the algorithm searches a genome database that contains 2,078,786 DNA sequences. It reported 258 potentially novel HIF-1 targets including 25 known HIF-1 targets. Based on microarray studies from the literature, 17 putative genes were confirmed to be upregulated by HIF-1 or hypoxia inside these 258 genes. We further studied one of the potential targets, COX-2, in the biological lab; and showed that it was a biologically relevant HIF-1 target. These results demonstrate that our methodology is an effective computational approach for identifying novel HIF-1 targets.

No MeSH data available.


Related in: MedlinePlus