A global genomic transcriptional code associated with CNS-expressed genes.
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.
Bailey
Peter J
PJ
Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institute, S-171, 77 Stockholm, Sweden.
Klos
Joanna M
JM
Andersson
Elisabet
E
Karlén
Mattias
M
Källström
Magdalena
M
Ponjavic
Jasmina
J
Muhr
Jonas
J
Lenhard
Boris
B
Sandelin
Albin
A
Ericson
Johan
J
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*
D006609:High Mobility Group Proteins; D018398:Homeodomain Proteins; D050809:POU Domain Factors