Conservation and regulatory associations of a wide affinity range of mouse transcription factor binding sites.
Identifieur interne : 001E58 ( PubMed/Checkpoint ); précédent : 001E57; suivant : 001E59Conservation 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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Berger</name></author><author><name sortKey="Stottmann, Rolf" sort="Stottmann, Rolf" uniqKey="Stottmann R" first="Rolf" last="Stottmann">Rolf Stottmann</name></author><author><name sortKey="Hughes, Timothy R" sort="Hughes, Timothy R" uniqKey="Hughes T" first="Timothy R" last="Hughes">Timothy R. Hughes</name></author><author><name sortKey="Bulyk, Martha L" sort="Bulyk, Martha L" uniqKey="Bulyk M" first="Martha L" last="Bulyk">Martha L. Bulyk</name></author></analytic><series><title level="j">Genomics</title><idno type="eISSN">1089-8646</idno><imprint><date when="2010" type="published">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Base Sequence (genetics)</term><term>Binding Sites (genetics)</term><term>CpG Islands (genetics)</term><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></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Analyse de séquence d'ADN</term><term>Analyse par réseau de protéines</term><term>Animaux</term><term>Facteurs de transcription (métabolisme)</term><term>Humains</term><term>Ilots CpG (génétique)</term><term>Régions promotrices (génétique) (génétique)</term><term>Régulation de l'expression des gènes</term><term>Sites de fixation (génétique)</term><term>Souris</term><term>Séquence nucléotidique (génétique)</term><term>Séquences d'acides nucléiques régulatrices (génétique)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Transcription Factors</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Base Sequence</term><term>Binding Sites</term><term>CpG Islands</term><term>Promoter Regions, Genetic</term><term>Regulatory Sequences, Nucleic Acid</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Ilots CpG</term><term>Régions promotrices (génétique)</term><term>Sites de fixation</term><term>Séquence nucléotidique</term><term>Séquences d'acides nucléiques régulatrices</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Facteurs de transcription</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Gene Expression Regulation</term><term>Humans</term><term>Mice</term><term>Protein Array Analysis</term><term>Sequence Analysis, DNA</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Analyse de séquence d'ADN</term><term>Analyse par réseau de protéines</term><term>Animaux</term><term>Humains</term><term>Régulation de l'expression des gènes</term><term>Souris</term></keywords></textClass></profileDesc></teiHeader><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></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">20079828</PMID><DateCompleted><Year>2010</Year><Month>07</Month><Day>08</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>13</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1089-8646</ISSN><JournalIssue CitedMedium="Internet"><Volume>95</Volume><Issue>4</Issue><PubDate><Year>2010</Year><Month>Apr</Month></PubDate></JournalIssue><Title>Genomics</Title><ISOAbbreviation>Genomics</ISOAbbreviation></Journal><ArticleTitle>Conservation and regulatory associations of a wide affinity range of mouse transcription factor binding sites.</ArticleTitle><Pagination><MedlinePgn>185-95</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.ygeno.2010.01.002</ELocationID><Abstract><AbstractText>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.</AbstractText><CopyrightInformation>Copyright 2010 Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Jaeger</LastName><ForeName>Savina A</ForeName><Initials>SA</Initials><AffiliationInfo><Affiliation>Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chan</LastName><ForeName>Esther T</ForeName><Initials>ET</Initials></Author><Author ValidYN="Y"><LastName>Berger</LastName><ForeName>Michael F</ForeName><Initials>MF</Initials></Author><Author ValidYN="Y"><LastName>Stottmann</LastName><ForeName>Rolf</ForeName><Initials>R</Initials></Author><Author ValidYN="Y"><LastName>Hughes</LastName><ForeName>Timothy R</ForeName><Initials>TR</Initials></Author><Author ValidYN="Y"><LastName>Bulyk</LastName><ForeName>Martha L</ForeName><Initials>ML</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 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Berger</name><name sortKey="Bulyk, Martha L" sort="Bulyk, Martha L" uniqKey="Bulyk M" first="Martha L" last="Bulyk">Martha L. Bulyk</name><name sortKey="Chan, Esther T" sort="Chan, Esther T" uniqKey="Chan E" first="Esther T" last="Chan">Esther T. Chan</name><name sortKey="Hughes, Timothy R" sort="Hughes, Timothy R" uniqKey="Hughes T" first="Timothy R" last="Hughes">Timothy R. Hughes</name><name sortKey="Stottmann, Rolf" sort="Stottmann, Rolf" uniqKey="Stottmann R" first="Rolf" last="Stottmann">Rolf Stottmann</name></noCountry><country name="États-Unis"><region name="Massachusetts"><name sortKey="Jaeger, Savina A" sort="Jaeger, Savina A" uniqKey="Jaeger S" first="Savina A" last="Jaeger">Savina A. Jaeger</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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