title: Conserved elements in Pax6 intron 7 involved in (auto)regulation and alternative transcription.
abstract: Pax6 is a transcription factor with an essential role in eye, central nervous system, and pancreas development. Its expression pattern is restricted to these specific domains within the developing embryo. Here four conserved elements are identified in Pax6 intron 7, showing a high level of sequence conservation between human, mouse, pufferfish, and zebrafish. Three of these are shown to act as cis-regulatory elements, directing expression of a reporter gene to distinct subsets of the Pax6 expression domain. CE1 regulates gene expression in late eye development, CE2 drives expression in the diencephalon and in the developing heart tube where Pax6 is not normally expressed, while CE3 directs expression in rhombencephalon. CE2 is shown to be autoregulated in the diencephalon, responding to absence of Pax6. We identify a highly conserved Pax6 recognition site and demonstrate its ability to bind Pax6 specifically. CE1 is embedded in a CpG island, and we identify a novel Pax6 transcript which initiates from this region. Functional analysis of evolutionary conserved sequences pinpoints novel cis-acting elements that govern the regulation of the complex spatio-temporal and quantitative expression of Pax6.
authors.affiliation: MRC Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, UK. dirkjan@hgu.mrc.ac.uk
authors.forename: Dirk A
authors.initials: DA
authors.lastname: Kleinjan
authors.forename: Anne
authors.initials: A
authors.lastname: Seawright
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Childs
authors.forename: Veronica
authors.initials: V
authors.lastname: van Heyningen
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004027:Diencephalon / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005136:Eye Proteins; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D007438:Introns; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009928:Organ Specificity; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D017422:Sequence Analysis, DNA
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins