Meta-analysis discovery of tissue-specific DNA sequence motifs from mammalian gene expression data.

BMC Bioinformatics
Bertrand R Huber, Martha L Bulyk

Abstract

A key step in the regulation of gene expression is the sequence-specific binding of transcription factors (TFs) to their DNA recognition sites. However, elucidating TF binding site (TFBS) motifs in higher eukaryotes has been challenging, even when employing cross-species sequence conservation. We hypothesized that for human and mouse, many orthologous genes expressed in a similarly tissue-specific manner in both human and mouse gene expression data, are likely to be co-regulated by orthologous TFs that bind to DNA sequence motifs present within noncoding sequence conserved between these genomes. We performed automated motif searching and merging across four different motif finding algorithms, followed by filtering of the resulting motifs for those that contain blocks of information content. Applying this motif finding strategy to conserved noncoding regions surrounding co-expressed tissue-specific human genes allowed us to discover both previously known, and many novel candidate, regulatory DNA motifs in all 18 tissue-specific expression clusters that we examined. For previously known TFBS motifs, we observed that if a TF was expressed in the specified tissue of interest, then in most cases we identified a motif that matched it...Continue Reading

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Citations

Aug 11, 2006·Nature Biotechnology·Patrik D'haeseleer
Mar 4, 2008·Nature Methods·Jason B WarnerMartha L Bulyk
Dec 17, 2008·Bioinformatics·Helge G RoiderStefan A Haas
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Sep 14, 2010·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Noboru J Sakabe, Marcelo A Nobrega

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Methods Mentioned

BETA
immunoprecipitation
phylogenetic footprinting
ChIP-chip
one-hybrid

Software Mentioned

TRANSFAC
Miner
BlockFilter
Perl script
RepeatMasked
RepeatMasker
XML
BioProspector
MotifSampler
AlignACE

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