title: Crx broadly modulates the pineal transcriptome.
abstract: Cone-rod homeobox (Crx) encodes Crx, a transcription factor expressed selectively in retinal photoreceptors and pinealocytes, the major cell type of the pineal gland. In this study, the influence of Crx on the mammalian pineal gland was studied by light and electron microscopy and by use of microarray and qRTPCR technology, thereby extending previous studies on selected genes (Furukawa et al. 1999). Deletion of Crx was not found to alter pineal morphology, but was found to broadly modulate the mouse pineal transcriptome, characterized by a>2-fold down-regulation of 543 genes and a>2-fold up-regulation of 745 genes (p<0.05). Of these, one of the most highly up-regulated (18-fold) was Hoxc4, a member of the Hox gene family, members of which are known to control gene expression cascades. During a 24-h period, a set of 51 genes exhibited differential day/night expression in pineal glands of wild-type animals; only eight of these were also day/night expressed in the Crx⁻/⁻ pineal gland. However, in the Crx⁻/⁻ pineal gland 41 genes exhibited differential night/day expression that was not seen in wild-type animals. These findings indicate that Crx broadly modulates the pineal transcriptome and also influences differential night/day gene expression in this tissue. Some effects of Crx deletion on the pineal transcriptome might be mediated by Hoxc4 up-regulation.
authors.affiliation: Department of Neuroscience and Pharmacology, Panum Institute, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Louise
authors.initials: L
authors.lastname: Rovsing
authors.forename: Samuel
authors.initials: S
authors.lastname: Clokie
authors.forename: Diego M
authors.initials: DM
authors.lastname: Bustos
authors.forename: Kristian
authors.initials: K
authors.lastname: Rohde
authors.forename: Steven L
authors.initials: SL
authors.lastname: Coon
authors.forename: Thomas
authors.initials: T
authors.lastname: Litman
authors.forename: Martin F
authors.initials: MF
authors.lastname: Rath
authors.forename: Morten
authors.initials: M
authors.lastname: Møller
authors.forename: David C
authors.initials: DC
authors.lastname: Klein
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology; D003001:Cloning, Molecular; D019295:Computational Biology; D003627:Data Interpretation, Statistical; D015536:Down-Regulation; D017353:Gene Deletion; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D046228:Microarray Analysis; D046529:Microscopy, Electron, Transmission; D010870:Pineal Gland / Q000033:anatomy & histology / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; C490904:Hoxc4 protein, mouse; D015534:Trans-Activators; C109288:cone rod homeobox protein