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Article: Evolution of the vertebrate gene regulatory network controlled by the transcriptional repressor REST

TitleEvolution of the vertebrate gene regulatory network controlled by the transcriptional repressor REST
Authors
KeywordsHuman-specific
Transcription factor binding
REST
RE1
Primate-specific
Primate
NRSF
Neural gene
Network
Motif
Lineage-specific
Gene regulation
Evolution
Issue Date2009
Citation
Molecular Biology and Evolution, 2009, v. 26, n. 7, p. 1491-1507 How to Cite?
AbstractSpecific wiring of gene-regulatory networks is likely to underlie much of the phenotypic difference between species, but the extent of lineage-specific regulatory architecture remains poorly understood. The essential vertebrate transcriptional repressor REST (RE1-Silencing Transcription Factor) targets many neural genes during development of the preimplantation embryo and the central nervous system, through its cognate DNA motif, the RE1 (Repressor Element 1). Here we present a comparative genomic analysis of REST recruitment in multiple species by integrating both sequence and experimental data. We use an accurate, experimentally validated Position-Specific Scoring Matrix method to identify REST binding sites in multiply aligned vertebrate genomes, allowing us to infer the evolutionary origin of each of 1,298 human RE1 elements. We validate these findings using exper imental data of REST binding across the whole genomes of human and mouse. We show that one-third of human RE1s are unique to primates: These sites recruit REST in vivo, target neural genes, and are under purifying evolutionary selection. We observe a consistent and significant trend for more ancient RE1s to have higher affinity for REST than lineage-specific sites and to be more proximal to target genes. Our results lead us to propose a model where new transcription factor binding sites are constantly generated throughout the genome; thereafter, refinement of their sequence and location consolidates this remodeling of networks governing neural gene regulation.
Persistent Identifierhttp://hdl.handle.net/10722/253137
ISSN
2020 Impact Factor: 16.24
2020 SCImago Journal Rankings: 6.637
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorJohnson, Rory-
dc.contributor.authorSamuel, John-
dc.contributor.authorNg, Calista Keow Leng-
dc.contributor.authorJauch, Ralf-
dc.contributor.authorStanton, Lawrence W.-
dc.contributor.authorWood, Ian C.-
dc.date.accessioned2018-05-11T05:38:42Z-
dc.date.available2018-05-11T05:38:42Z-
dc.date.issued2009-
dc.identifier.citationMolecular Biology and Evolution, 2009, v. 26, n. 7, p. 1491-1507-
dc.identifier.issn0737-4038-
dc.identifier.urihttp://hdl.handle.net/10722/253137-
dc.description.abstractSpecific wiring of gene-regulatory networks is likely to underlie much of the phenotypic difference between species, but the extent of lineage-specific regulatory architecture remains poorly understood. The essential vertebrate transcriptional repressor REST (RE1-Silencing Transcription Factor) targets many neural genes during development of the preimplantation embryo and the central nervous system, through its cognate DNA motif, the RE1 (Repressor Element 1). Here we present a comparative genomic analysis of REST recruitment in multiple species by integrating both sequence and experimental data. We use an accurate, experimentally validated Position-Specific Scoring Matrix method to identify REST binding sites in multiply aligned vertebrate genomes, allowing us to infer the evolutionary origin of each of 1,298 human RE1 elements. We validate these findings using exper imental data of REST binding across the whole genomes of human and mouse. We show that one-third of human RE1s are unique to primates: These sites recruit REST in vivo, target neural genes, and are under purifying evolutionary selection. We observe a consistent and significant trend for more ancient RE1s to have higher affinity for REST than lineage-specific sites and to be more proximal to target genes. Our results lead us to propose a model where new transcription factor binding sites are constantly generated throughout the genome; thereafter, refinement of their sequence and location consolidates this remodeling of networks governing neural gene regulation.-
dc.languageeng-
dc.relation.ispartofMolecular Biology and Evolution-
dc.subjectHuman-specific-
dc.subjectTranscription factor binding-
dc.subjectREST-
dc.subjectRE1-
dc.subjectPrimate-specific-
dc.subjectPrimate-
dc.subjectNRSF-
dc.subjectNeural gene-
dc.subjectNetwork-
dc.subjectMotif-
dc.subjectLineage-specific-
dc.subjectGene regulation-
dc.subjectEvolution-
dc.titleEvolution of the vertebrate gene regulatory network controlled by the transcriptional repressor REST-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1093/molbev/msp058-
dc.identifier.pmid19318521-
dc.identifier.scopuseid_2-s2.0-67649313831-
dc.identifier.volume26-
dc.identifier.issue7-
dc.identifier.spage1491-
dc.identifier.epage1507-
dc.identifier.eissn1537-1719-
dc.identifier.isiWOS:000266966200008-
dc.identifier.issnl0737-4038-

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