ZIFIBI: Prediction of DNA binding sites for zinc finger proteins

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Abstract

The cis-regulatory region of target genes is key elements in the transcriptional regulation of gene expression. Many of these cis-regulatory regions have not been identified by either biological experiments or computational methods. Recently, a few additional C2H2 zinc finger transcription factor binding sites have been discovered. The majority of the zinc finger binding sites, however, are still unknown. In this study, we used publically available data to evaluate possible interaction patterns between nucleotides and the amino acids of zinc finger domains. We calculated the most probable state path of three nucleotides sequences using a Hidden Markov Model (HMM). We used these computations to predict C2H2 zinc finger transcription factor binding sites in cis-regulatory regions of their target genes (http://bioinfo.hanyang.ac.kr/ZIFIBI/frameset.php).

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Materials and methods

Construction of binding information (Position Weighted Matrix). To quantify the interaction between the 3 nucleotides and amino acids in positions −1, 3, and 6 of the C2H2 zinc finger domain [7], we searched publically available data for zinc finger binding sites and found 187 C2H2 zinc finger domains verified by previous biochemical experiments [11], [12], [13], [14]. These C2H2 domains could potentially interact with 45 different combinations of 3 bp long nucleotide sequences.

Using the

Results

To predict the DNA binding site of the C2H2 zinc finger domain, we obtained specific amino acid sequences from SWISS-PROT for 1108 proteins that contain more than two C2H2 zinc finger domains [16]. We used the C2H2 conserved pattern (C–X(2–5)–C–X(3)–(F/Y/)–X(8)–H–X(3–5)–H) of 952 of the proteins for the identification of amino acids in positions −1, 3, and 6 in the C2H2 zinc finger domain [17], [18]. It was not possible to identify the amino acids in 156 of the proteins because they did not

Discussion

The ZIFIBI database we created contains proteins with potential binding sites for zinc finger proteins that have not yet been experimentally identified. We compared ZIFIBI with three other studies in which DNA binding site predictions for C2H2 zinc finger domains were made. TRANSFAC, one of the databases used for comparison, includes 28 binding matrices for C2H2 zinc finger proteins. The average Euclidean distance of ZIFIBI was 0.613929, which is lower than those found in other studies

Web interfaces

ZIFIBI provides DNA binding site information for C2H2 zinc finger proteins and provides convenient computational methods to search for target genes.

  • 1.

    Function to search DNA binding sites: ZIFIBI has a searching function by gene name, SWISS-PROT ID or SWISS-PROT access number for specific protein.

  • 2.

    Function to search target genes: ZIFIBI has target gene list for C2H2 zinc finger proteins and binding sites in the 2.1 kb promoter region of target gene.

ZIFIBI provides information that will further our

Acknowledgment

This work was supported in part by Ministry of Science and Technology (MOST) Grants (M10411010001-06O1101-00110).

References (21)

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1

Present address: DNA Link Inc., Seoul, Republic of Korea.

2

Present address: Korean Bioinformation Center, KRIBB, Republic of Korea.

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