title: A global genomic transcriptional code associated with CNS-expressed genes.
abstract: Highly conserved non-coding DNA regions (HCNR) occur frequently in vertebrate genomes, but their functional roles remain unclear. Here, we provide evidence that a large portion of HCNRs are enriched for binding sites for Sox, POU and Homeodomain transcription factors, and such HCNRs can act as cis-regulatory regions active in neural stem cells. Strikingly, these HCNRs are linked to several hundreds of genes expressed in the developing CNS and they may exert locus-wide regulatory effects on multiple genes flanking their genomic location. Moreover, these data imply a unifying transcriptional logic for a large set of CNS-expressed genes in which Sox and POU proteins act as generic promoters of transcription while Homeodomain proteins control the spatial expression of genes through active repression.
authors.affiliation: Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institute, S-171, 77 Stockholm, Sweden.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Bailey
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Klos
authors.forename: Elisabet
authors.initials: E
authors.lastname: Andersson
authors.forename: Mattias
authors.initials: M
authors.lastname: Karlén
authors.forename: Magdalena
authors.initials: M
authors.lastname: Källström
authors.forename: Jasmina
authors.initials: J
authors.lastname: Ponjavic
authors.forename: Jonas
authors.initials: J
authors.lastname: Muhr
authors.forename: Boris
authors.initials: B
authors.lastname: Lenhard
authors.forename: Albin
authors.initials: A
authors.lastname: Sandelin
authors.forename: Johan
authors.initials: J
authors.lastname: Ericson
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D019521:Body Patterning / Q000235:genetics; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism*; D002642:Chick Embryo; D017124:Conserved Sequence / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D016678:Genome / Q000235:genetics*; D023281:Genomics; D006609:High Mobility Group Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D050809:POU Domain Factors / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D023721:Tetraodontiformes / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D006609:High Mobility Group Proteins; D018398:Homeodomain Proteins; D050809:POU Domain Factors