Conservation and regulatory associations of a wide affinity range of mouse transcription factor binding sites.
Identifieur interne : 000731 ( Ncbi/Checkpoint ); précédent : 000730; suivant : 000732Conservation and regulatory associations of a wide affinity range of mouse transcription factor binding sites.
Auteurs : Savina A. Jaeger [États-Unis] ; Esther T. Chan ; Michael F. Berger ; Rolf Stottmann ; Timothy R. Hughes ; Martha L. BulykSource :
- Genomics [ 1089-8646 ] ; 2010.
Descripteurs français
- KwdFr :
- Analyse de séquence d'ADN, Analyse par réseau de protéines, Animaux, Facteurs de transcription (métabolisme), Humains, Ilots CpG (génétique), Régions promotrices (génétique) (génétique), Régulation de l'expression des gènes, Sites de fixation (génétique), Souris, Séquence nucléotidique (génétique), Séquences d'acides nucléiques régulatrices (génétique).
- MESH :
- génétique : Ilots CpG, Régions promotrices (génétique), Sites de fixation, Séquence nucléotidique, Séquences d'acides nucléiques régulatrices.
- métabolisme : Facteurs de transcription.
- Analyse de séquence d'ADN, Analyse par réseau de protéines, Animaux, Humains, Régulation de l'expression des gènes, Souris.
English descriptors
- KwdEn :
- MESH :
- chemical , metabolism : Transcription Factors.
- genetics : Base Sequence, Binding Sites, CpG Islands, Promoter Regions, Genetic, Regulatory Sequences, Nucleic Acid.
- Animals, Gene Expression Regulation, Humans, Mice, Protein Array Analysis, Sequence Analysis, DNA.
Abstract
Sequence-specific binding by transcription factors (TFs) interprets regulatory information encoded in the genome. Using recently published universal protein binding microarray (PBM) data on the in vitro DNA binding preferences of these proteins for all possible 8-base-pair sequences, we examined the evolutionary conservation and enrichment within putative regulatory regions of the binding sequences of a diverse library of 104 nonredundant mouse TFs spanning 22 different DNA-binding domain structural classes. We found that not only high affinity binding sites, but also numerous moderate and low affinity binding sites, are under negative selection in the mouse genome. These 8-mers occur preferentially in putative regulatory regions of the mouse genome, including CpG islands and non-exonic ultraconserved elements (UCEs). Of TFs whose PBM "bound" 8-mers are enriched within sets of tissue-specific UCEs, many are expressed in the same tissue(s) as the UCE-driven gene expression. Phylogenetically conserved motif occurrences of various TFs were also enriched in the noncoding sequence surrounding numerous gene sets corresponding to Gene Ontology categories and tissue-specific gene expression clusters, suggesting involvement in transcriptional regulation of those genes. Altogether, our results indicate that many of the sequences bound by these proteins in vitro, including lower affinity DNA sequences, are likely to be functionally important in vivo. This study not only provides an initial analysis of the potential regulatory associations of 104 mouse TFs, but also presents an approach for the functional analysis of TFs from any other metazoan genome as their DNA binding preferences are determined by PBMs or other technologies.
DOI: 10.1016/j.ygeno.2010.01.002
PubMed: 20079828
Affiliations:
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pubmed:20079828Le document en format XML
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<term>Gene Expression Regulation</term>
<term>Humans</term>
<term>Mice</term>
<term>Promoter Regions, Genetic (genetics)</term>
<term>Protein Array Analysis</term>
<term>Regulatory Sequences, Nucleic Acid (genetics)</term>
<term>Sequence Analysis, DNA</term>
<term>Transcription Factors (metabolism)</term>
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<term>Humains</term>
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<term>Régions promotrices (génétique) (génétique)</term>
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<term>Sites de fixation (génétique)</term>
<term>Souris</term>
<term>Séquence nucléotidique (génétique)</term>
<term>Séquences d'acides nucléiques régulatrices (génétique)</term>
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<term>Binding Sites</term>
<term>CpG Islands</term>
<term>Promoter Regions, Genetic</term>
<term>Regulatory Sequences, Nucleic Acid</term>
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<term>Séquence nucléotidique</term>
<term>Séquences d'acides nucléiques régulatrices</term>
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<term>Humans</term>
<term>Mice</term>
<term>Protein Array Analysis</term>
<term>Sequence Analysis, DNA</term>
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<term>Analyse par réseau de protéines</term>
<term>Animaux</term>
<term>Humains</term>
<term>Régulation de l'expression des gènes</term>
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<front><div type="abstract" xml:lang="en">Sequence-specific binding by transcription factors (TFs) interprets regulatory information encoded in the genome. Using recently published universal protein binding microarray (PBM) data on the in vitro DNA binding preferences of these proteins for all possible 8-base-pair sequences, we examined the evolutionary conservation and enrichment within putative regulatory regions of the binding sequences of a diverse library of 104 nonredundant mouse TFs spanning 22 different DNA-binding domain structural classes. We found that not only high affinity binding sites, but also numerous moderate and low affinity binding sites, are under negative selection in the mouse genome. These 8-mers occur preferentially in putative regulatory regions of the mouse genome, including CpG islands and non-exonic ultraconserved elements (UCEs). Of TFs whose PBM "bound" 8-mers are enriched within sets of tissue-specific UCEs, many are expressed in the same tissue(s) as the UCE-driven gene expression. Phylogenetically conserved motif occurrences of various TFs were also enriched in the noncoding sequence surrounding numerous gene sets corresponding to Gene Ontology categories and tissue-specific gene expression clusters, suggesting involvement in transcriptional regulation of those genes. Altogether, our results indicate that many of the sequences bound by these proteins in vitro, including lower affinity DNA sequences, are likely to be functionally important in vivo. This study not only provides an initial analysis of the potential regulatory associations of 104 mouse TFs, but also presents an approach for the functional analysis of TFs from any other metazoan genome as their DNA binding preferences are determined by PBMs or other technologies.</div>
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