title: The Optimedin gene is a downstream target of Pax6.
abstract: The Optimedin gene, also known as Olfactomedin 3, encodes an olfactomedin domain-containing protein. There are two major splice variants of the Optimedin mRNA, Optimedin A and Optimedin B, transcribed from different promoters. The expression pattern of the Optimedin A variant in the eye and brain overlaps with that for Pax6, which encodes a protein containing the paired and homeobox DNA-binding domains. The Pax6 gene plays a critical role for the development of eyes, central nervous system, and endocrine glands. The proximal promoter of the Optimedin A variant contains a putative Pax6 binding site in position -86/-70. Pax6 binds this site through the paired domain in vitro as judged by electrophoretic mobility shift assay. Mutations in this site eliminate Pax6 binding as well as stimulation of the Optimedin promoter activity by Pax6 in transfection experiments. Pax6 occupies the binding site in the proximal promoter in vivo as demonstrated by the chromatin immunoprecipitation assay. Altogether these results identify the Optimedin gene as a downstream target regulated by Pax6. Although the function of optimedin is still not clear, it is suggested to be involved in cell-cell adhesion and cell attachment to the extracellular matrix. Pax6 regulation of Optimedin in the eye and brain may directly affect multiple developmental processes, including cell migration and axon growth.
authors.affiliation: Section of Molecular Mechanisms of Glaucoma, Laboratory of Molecular and Developmental Biology, NEI, National Institutes of Health, Bethesda, Maryland 20892-0704, USA.
authors.forename: Oleg
authors.initials: O
authors.lastname: Grinchuk
authors.forename: Zbynek
authors.initials: Z
authors.lastname: Kozmik
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Wu
authors.forename: Stanislav
authors.initials: S
authors.lastname: Tomarev
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D001921:Brain / Q000196:embryology; D019556:COS Cells; D002448:Cell Adhesion; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D002843:Chromatin / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis* / Q000235:genetics*; D005123:Eye / Q000196:embryology; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics*; D024002:HMGB Proteins / Q000378:metabolism; D006609:High Mobility Group Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008957:Models, Genetic; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000071841:PAX6 Transcription Factor; D050809:POU Domain Factors / Q000378:metabolism; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D055748:SOXB1 Transcription Factors; D055751:SOXC Transcription Factors; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D002843:Chromatin; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D016326:Extracellular Matrix Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D024002:HMGB Proteins; D006609:High Mobility Group Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; C466064:OLFM3 protein, human; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D050809:POU Domain Factors; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; C000605733:Pax6 protein, rat; D012333:RNA, Messenger; D012097:Repressor Proteins; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D055751:SOXC Transcription Factors; C490793:Sox11 protein, mouse; C527783:Sox2 protein, mouse; C527784:Sox2 protein, rat; D015534:Trans-Activators; D014157:Transcription Factors; C074065:Pou3f3 protein, mouse; D008156:Luciferases