PATTERNFINDER: combined analysis of DNA regulatory sequences and double-helix stability

Yanlin Huang,David Kowalski

doi:10.1186/1471-2105-5-134

Abstract

BackgroundRegulatory regions that function in DNA replication and gene transcription contain specific sequences that bind proteins as well as less-specific sequences in which the double helix is often easy to unwind. Progress towards predicting and characterizing regulatory regions could be accelerated by computer programs that perform a combined analysis of specific sequences and DNA unwinding properties.ResultsHere we present PATTERNFINDER, a web server that searches DNA sequences for matches to specific or flexible patterns, and analyzes DNA helical stability. A batch mode of the program generates a tabular map of matches to multiple, different patterns. Regions flanking pattern matches can be targeted for helical stability analysis to identify sequences with a minimum free energy for DNA unwinding. As an example application, we analyzed a regulatory region of the human c-myc proto-oncogene consisting of a single-strand-specific protein binding site within a DNA region that unwindsin vivo. The predicted region of minimal helical stability overlapped both the protein binding site and the unwound DNA region identified experimentally.ConclusionsThe PATTERNFINDER web server permits localization of known functional elements or landmarks in DNA sequences as well as prediction of potential new elements. Batch analysis of multiple patterns facilitates the annotation of DNA regulatory regions. Identifying specific pattern matches linked to DNA with low helical stability is useful in characterizing regulatory regions for transcription, replication and other processes and may predict functional DNA unwinding elements.PATTERNFINDER can be accessed freely at:

Highlights

Regulatory regions that function in DNA replication and gene transcription contain specific sequences that bind proteins as well as less-specific sequences in which the double helix is often easy to unwind
Low helical stability of DNA is of general importance since it is a feature of regulatory sequences involved in a variety of cellular processes including gene transcription, replication, nuclear matrix attachment and DNA repeat instability [6,10,12,13,14]
Examples of specific patterns include sequences known to be recognized by particular proteins or enzymes, or sequences complementary to oligonucleotide primers

Summary

Introduction

Regulatory regions that function in DNA replication and gene transcription contain specific sequences that bind proteins as well as less-specific sequences in which the double helix is often easy to unwind. DNA unwinding, flexibility and topology are important in regulating gene transcription and other processes [2]. Mutational analysis has revealed a functional region of low helical stability, called a DNA unwinding element, in replication origins in several species [6,7,8,9]. Low helical stability of DNA is of general importance since it is a feature of regulatory sequences involved in a variety of cellular processes including gene transcription, replication, nuclear matrix attachment and DNA repeat instability [6,10,12,13,14]

Results

Discussion

Conclusion