Of eyes and embryos subfunctionalization of the CRX homeobox gene in mammalian evolution
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ABSTRACT:
PROVIDER: PRJNA531409 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8864200_1.fastq.gz | Fastqsanger.gz | |||
| SRR8864200_2.fastq.gz | Fastqsanger.gz | |||
| SRR8864201_1.fastq.gz | Fastqsanger.gz | |||
| SRR8864201_2.fastq.gz | Fastqsanger.gz | |||
| SRR8864202_1.fastq.gz | Fastqsanger.gz |
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Project description:We have ectopically expressed two V5-tagged homeobox genes and a control plasmid in mouse embryonic fibroblasts. Following ectopic expression and chemical selection we used whole transcriptome sequencing to reveal any effect of forced missed expression on the MEF transcriptome.
2020-04-13 | GSE129456 | GEO
Project description:ETCHbox genes are fast-evolving homeobox genes present only in eutherian (placental) mammals which originated by duplication and divergence from a conserved homeobox gene, Cone-rod homeobox (CRX). While expression and function of CRX are restricted to the retina in eutherian mammals, ETCHbox gene expression is specific to preimplantation embryos. This dramatic difference could reflect the acquisition of new functions by duplicated genes or subfunctionalization of pleiotropic roles between CRX and ETCHbox genes. To resolve between these hypotheses, we compared expression, sequence and inferred function between CRX of metatherian (marsupial) mammals and ETCHbox genes of eutherians. We find the metatherian CRX homeobox gene is expressed in early embryos and in eyes, unlike eutherian CRX, and distinct amino acid substitutions were fixed in the metatherian and eutherian evolutionary lineages consistent with altered transcription factor specificity. We find that metatherian CRX is capable of regulating embryonically expressed genes in cultured cells in a comparable way to eutherian ETCHbox. The data are consistent with CRX having a dual role in eyes and embryos of metatherians, providing an early embryonic function comparable to that of eutherian ETCHbox genes; we propose that subfunctionalization of pleiotropic functions occurred after gene duplication along the placental lineage, followed by functional elaboration.
| S-EPMC6661347 | biostudies-literature
Project description:To investigate the role of the circadian clock of the photoreceptor cells in regulation of retinal protein rhythms, we have analyzed diurnal protein expression in the photoreceptor-deficient cone-rod homeobox knock out mouse (Crx-/-). Retinal homogenates of 129/sv and Crx-/- mice were analysed by 2D-PAGE. Differentially expressed spots were in-gel digested with trypsin and identified by LC-MS/MS. Data were used to search the Swiss-Prot protein database.
2017-04-04 | PXD005556 | Pride
Project description:The cone-rod homeobox gene (Crx) encodes Crx, a transcription factor selectively expressed in two cell types, retinal photoreceptors and the melatonin secreting pinealocytes of the pineal gland. In this report the role of Crx in regulating gene expression in the mammalian pineal gland was extended using Affymetrix GeneChip technology. Deletion of Crx results in broad modulation of the mouse pineal transcriptome, including a >2-fold downregulation of 543 genes and a >2-fold upregulation of 745 genes. In addition to Crx, there was a >10-fold downregulation of 13 other genes. Of special interest was the discovery of a link between Crx and the homeobox gene Hoxc4, which was upregulated ~20-fold in the Crx-/- pineal gland. Analysis of night and day expression of genes indicated that a set of 51 genes exhibited differential expression in control animals. Of these genes, only eight were also differentially expressed in Crx-/- animals. This group included Aanat, which encodes the enzyme that controls the daily rhythm in melatonin synthesis in the vertebrate pineal gland. Accordingly, Crx appears to be essential for the 24-hour rhythmic component of expression of some genes in the pineal gland. In the Crx-/- mouse pineal gland, 41 genes exhibited differential night/day expression that was not seen in control animals, suggesting that Crx may function to modulate rhythmic expression of these genes as well. Together, the results of this investigation indicate that Crx broadly modulates the pineal transcriptome, perhaps in part through suppressive effects on expression of the homeobox gene Hoxc4. Pineal glands from control (129sv) mice and Crx-/- mice were collected at ZT6 and ZT20 for RNA extraction and hybridization on Affymetrix mouse 430_2 chip. Each condition were performed as triplicats. SUPPLEMENTARY FILES: The GCOS signal intensity data were analyzed using ChipInspector (Genomatix) version 2.1. FDR= 0, p-value <0.05, cut off=1, region size = 300 bp and 4 and 5 significant probes. Log(2) fold change independently of time of day. Up regulated genes: genes which are up regulated in Crx-/- compared to the control; down regulated genes: genes which are down regulated in Crx-/- compared to the control.
2012-01-01 | E-GEOD-24625 | biostudies-arrayexpress
Project description:The cone-rod homeobox gene (Crx) encodes Crx, a transcription factor selectively expressed in two cell types, retinal photoreceptors and the melatonin secreting pinealocytes of the pineal gland. In this report the role of Crx in regulating gene expression in the mammalian pineal gland was extended using Affymetrix GeneChip technology. Deletion of Crx results in broad modulation of the mouse pineal transcriptome, including a >2-fold downregulation of 543 genes and a >2-fold upregulation of 745 genes. In addition to Crx, there was a >10-fold downregulation of 13 other genes. Of special interest was the discovery of a link between Crx and the homeobox gene Hoxc4, which was upregulated ~20-fold in the Crx-/- pineal gland. Analysis of night and day expression of genes indicated that a set of 51 genes exhibited differential expression in control animals. Of these genes, only eight were also differentially expressed in Crx-/- animals. This group included Aanat, which encodes the enzyme that controls the daily rhythm in melatonin synthesis in the vertebrate pineal gland. Accordingly, Crx appears to be essential for the 24-hour rhythmic component of expression of some genes in the pineal gland. In the Crx-/- mouse pineal gland, 41 genes exhibited differential night/day expression that was not seen in control animals, suggesting that Crx may function to modulate rhythmic expression of these genes as well. Together, the results of this investigation indicate that Crx broadly modulates the pineal transcriptome, perhaps in part through suppressive effects on expression of the homeobox gene Hoxc4.
2012-01-01 | GSE24625 | GEO
Project description:Cone-Rod Homeobox, encoded by CRX, is a transcription factor (TF) essential for the terminal differentiation and maintenance of mammalian photoreceptors. Although a handful of human variants in CRX have been shown to cause several different degenerative retinopathies with varying cone and rod predominance, as with most human disease genes the vast majority of observed CRX genetic variants are uncharacterized variants of uncertain significance (VUS). We performed a deep mutational scan (DMS) of nearly all possible single amino acid substitution variants in CRX, using an engineered cell-based transcriptional reporter assay. We measured the ability of each CRX missense variant to transactivate a synthetic fluorescent reporter construct in a pooled fluorescence-activated cell sorting assay and compared the activation strength of each variant to that of wild-type CRX to compute an activity score, identifying thousands of variants with altered transcriptional activity.
2024-03-21 | GSE262060 | GEO
Project description:Mutations in the cone-rod homeobox (CRX) transcription factor lead to distinct retinopathy phenotypes, including early-onset vision impairment in dominant Leber congenital amaurosis (LCA). Using induced pluripotent stem cells (iPSCs) from a patient with CRX-I138fs mutation, we established an in vitro model of CRX-LCA in retinal organoids that exhibit defective photoreceptor maturation by histology and gene profiling including diminished expression of visual opsins. Gene therapy by delivery of an additional correct CRX allele using an AAV vector partially restored photoreceptor phenotype and expression of phototransduction-related genes as revealed by single cell RNA-sequencing. Retinal organoids derived from iPSCs of a second dominant CRX-LCA patient carrying a K88N mutation revealed loss of opsin expression as a common phenotype, which could also be alleviated by AAV-mediated overexpression of CRX. Our studies provide the proof-of-concept for development of gene therapy for dominant CRX-LCA and other CRX-retinopathies.
2021-02-17 | GSE153099 | GEO
Project description:Mutations in the cone-rod homeobox (CRX) transcription factor lead to distinct retinopathy phenotypes, including early-onset vision impairment in dominant Leber congenital amaurosis (LCA). Using induced pluripotent stem cells (iPSCs) from a patient with CRX-I138fs mutation, we established an in vitro model of CRX-LCA in retinal organoids that exhibit defective photoreceptor maturation by histology and gene profiling including diminished expression of visual opsins. Gene therapy by delivery of an additional correct CRX allele using an AAV vector partially restored photoreceptor phenotype and expression of phototransduction-related genes as revealed by single cell RNA-sequencing. Retinal organoids derived from iPSCs of a second dominant CRX-LCA patient carrying a K88N mutation revealed loss of opsin expression as a common phenotype, which could also be alleviated by AAV-mediated overexpression of CRX. Our studies provide the proof-of-concept for development of gene therapy for dominant CRX-LCA and other CRX-retinopathies.
2021-02-17 | GSE152939 | GEO
Project description:Retina-specific gene expression is the distinguishing characteristic of Group 3 medulloblastoma. CRX, a homeobox transcription factor, is overexpressed specifically in Group 3 tumors. ShRNA-mediated CRX knockdown decreased the expression of seveal retina-specific genes and Group 3 specific genes. CRX knockdown inhibited the TGF-beta/activin signaling pathway, which is known to play oncogenic role in a subset of Group 3 medulloblastoma
2021-08-26 | GSE174620 | GEO
Project description:ETCHbox genes are mammalian-specific PRD class homeobox genes with conserved expression in the preimplantation embryo but fast-evolving and highly divergent sequences. We ectopically expressed bovine ARGFX and LEUTX ETCHbox genes, both tagged with 3xFLAG tags, in bovine foetal fibroblasts and completed transcriptome seqencing. We compared the transcriptome of cells with ARGFX or LEUTX ectopic expression with control transfected cells. For ARGFX, we expressed the WT version of the gene and a mutant allele containing a 13bp frameshift deletion.
2022-05-24 | GSE192356 | GEO