Abstract

BackgroundAn important step in understanding the conditions that specify gene expression is the recognition of gene regulatory elements. Due to high diversity of different types of transcription factors and their DNA binding preferences, it is a challenging problem to establish an accurate model for recognition of functional regulatory elements in promoters of eukaryotic genes.ResultsWe present a method for precise prediction of a large group of transcription factor binding sites – steroid hormone response elements. We use a large training set of experimentally confirmed steroid hormone response elements, and adapt a sequence-based statistic method of position weight matrix, for identification of the binding sites in the query sequences. To estimate the accuracy level, a table of correspondence of sensitivity vs. specificity values is constructed from a number of independent tests. Furthermore, feed-forward neural network is used for cross-verification of the predicted response elements on genomic sequences.ConclusionThe proposed method demonstrates high accuracy level, and therefore can be used for prediction of hormone response elements de novo. Experimental results support our analysis by showing significant improvement of the proposed method over previous HRE recognition methods.

Highlights

  • An important step in understanding the conditions that specify gene expression is the recognition of gene regulatory elements

  • We examined the specific structure of binding sites of interest, which requires investigation of biological nature of hormone receptors

  • Verified hormone response elements (HRE) are used for training the statistic model The data was collected from more than 200 literature sources and our in-house wet-lab experiments

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Summary

Introduction

An important step in understanding the conditions that specify gene expression is the recognition of gene regulatory elements. Due to high diversity of different types of transcription factors and their DNA binding preferences, it is a challenging problem to establish an accurate model for recognition of functional regulatory elements in promoters of eukaryotic genes. Cancer treatment on early stages of tumor development is often associated with action of steroid hormones – progesterone [1] and estrogen [2]. Steroid hormones are believed to play an important role in the regulation of the development of breast cancer [3]. The molecular effects of estrogen and progesterone are reflected by their receptor-regulated gene expression [5]. The overall mechanism of the gene expression regulation by steroid hormones in a cell does include several stages of reaction,

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