Identification of Conserved Regulatory Elements in Mammalian Promoter Regions: a Case Study Using the PCK1 Promoter

Overview

Journal Genomics Proteomics Bioinformatics

Specialty Biology

Date 2009 Mar 31

PMID 19329064

Citations 8

Authors

George E Liu

Matthew T Weirauch

Curtis P Van Tassell

Robert W Li

Tad S Sonstegard

Lakshmi K Matukumalli

Erin E Connor

Richard W Hanson

Jianqi Yang

Affiliations

Soon will be listed here.

Abstract

A systematic phylogenetic footprinting approach was performed to identify conserved transcription factor binding sites (TFBSs) in mammalian promoter regions using human, mouse and rat sequence alignments. We found that the score distributions of most binding site models did not follow the Gaussian distribution required by many statistical methods. Therefore, we performed an empirical test to establish the optimal threshold for each model. We gauged our computational predictions by comparing with previously known TFBSs in the PCK1 gene promoter of the cytosolic isoform of phosphoenolpyruvate carboxykinase, and achieved a sensitivity of 75% and a specificity of approximately 32%. Almost all known sites overlapped with predicted sites, and several new putative TFBSs were also identified. We validated a predicted SP1 binding site in the control of PCK1 transcription using gel shift and reporter assays. Finally, we applied our computational approach to the prediction of putative TFBSs within the promoter regions of all available RefSeq genes. Our full set of TFBS predictions is freely available at http://bfgl.anri.barc.usda.gov/tfbsConsSites.

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