A novel unbiased measure for motif co-occurrence predicts combinatorial regulation of transcription

<p>Abstract</p> <p>Background</p> <p>Multiple transcription factors (TFs) are involved in the generation of gene expression patterns, such as tissue-specific gene expression and pleiotropic immune responses. However, how combinations of TFs orchestrate diverse gene expr...

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Main Authors: Vandenbon Alexis, Kumagai Yutaro, Akira Shizuo, Standley Daron M
Format: Article
Language:English
Published: BMC 2012-12-01
Series:BMC Genomics
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spelling doaj-9350f0aad3674d2b911f06a296354eeb2020-11-25T01:03:12ZengBMCBMC Genomics1471-21642012-12-0113Suppl 7S1110.1186/1471-2164-13-S7-S11A novel unbiased measure for motif co-occurrence predicts combinatorial regulation of transcriptionVandenbon AlexisKumagai YutaroAkira ShizuoStandley Daron M<p>Abstract</p> <p>Background</p> <p>Multiple transcription factors (TFs) are involved in the generation of gene expression patterns, such as tissue-specific gene expression and pleiotropic immune responses. However, how combinations of TFs orchestrate diverse gene expression patterns is poorly understood. Here we propose a new measure for regulatory motif co-occurrence and a new methodology to systematically identify TF pairs significantly co-occurring in a set of promoter sequences.</p> <p>Results</p> <p>Initial analyses suggest that non-CpG promoters have a higher potential for combinatorial regulation than CpG island-associated promoters, and that co-occurrences are strongly influenced by motif similarity. We applied our method to large-scale gene expression data from various tissues, and showed how our measure for motif co-occurrence is not biased by motif over-representation. Our method identified, amongst others, the binding motifs of HNF1 and FOXP1 to be significantly co-occurring in promoters of liver/kidney specific genes. Binding sites tend to be positioned proximally to each other, suggesting interactions exist between this pair of transcription factors. Moreover, the binding sites of several TFs were found to co-occur with NF-κB and IRF sites in sets of genes with similar expression patterns in dendritic cells after Toll-like receptor stimulation. Of these, we experimentally verified that CCAAT enhancer binding protein alpha positively regulates its target promoters synergistically with NF-κB.</p> <p>Conclusions</p> <p>Both computational and experimental results indicate that the proposed method can clarify TF interactions that could not be observed by currently available prediction methods.</p>
collection DOAJ
language English
format Article
sources DOAJ
author Vandenbon Alexis
Kumagai Yutaro
Akira Shizuo
Standley Daron M
spellingShingle Vandenbon Alexis
Kumagai Yutaro
Akira Shizuo
Standley Daron M
A novel unbiased measure for motif co-occurrence predicts combinatorial regulation of transcription
BMC Genomics
author_facet Vandenbon Alexis
Kumagai Yutaro
Akira Shizuo
Standley Daron M
author_sort Vandenbon Alexis
title A novel unbiased measure for motif co-occurrence predicts combinatorial regulation of transcription
title_short A novel unbiased measure for motif co-occurrence predicts combinatorial regulation of transcription
title_full A novel unbiased measure for motif co-occurrence predicts combinatorial regulation of transcription
title_fullStr A novel unbiased measure for motif co-occurrence predicts combinatorial regulation of transcription
title_full_unstemmed A novel unbiased measure for motif co-occurrence predicts combinatorial regulation of transcription
title_sort novel unbiased measure for motif co-occurrence predicts combinatorial regulation of transcription
publisher BMC
series BMC Genomics
issn 1471-2164
publishDate 2012-12-01
description <p>Abstract</p> <p>Background</p> <p>Multiple transcription factors (TFs) are involved in the generation of gene expression patterns, such as tissue-specific gene expression and pleiotropic immune responses. However, how combinations of TFs orchestrate diverse gene expression patterns is poorly understood. Here we propose a new measure for regulatory motif co-occurrence and a new methodology to systematically identify TF pairs significantly co-occurring in a set of promoter sequences.</p> <p>Results</p> <p>Initial analyses suggest that non-CpG promoters have a higher potential for combinatorial regulation than CpG island-associated promoters, and that co-occurrences are strongly influenced by motif similarity. We applied our method to large-scale gene expression data from various tissues, and showed how our measure for motif co-occurrence is not biased by motif over-representation. Our method identified, amongst others, the binding motifs of HNF1 and FOXP1 to be significantly co-occurring in promoters of liver/kidney specific genes. Binding sites tend to be positioned proximally to each other, suggesting interactions exist between this pair of transcription factors. Moreover, the binding sites of several TFs were found to co-occur with NF-κB and IRF sites in sets of genes with similar expression patterns in dendritic cells after Toll-like receptor stimulation. Of these, we experimentally verified that CCAAT enhancer binding protein alpha positively regulates its target promoters synergistically with NF-κB.</p> <p>Conclusions</p> <p>Both computational and experimental results indicate that the proposed method can clarify TF interactions that could not be observed by currently available prediction methods.</p>
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