GEO DataSets

(Submitter supplied) P10 retinal gene expression analysis of the homozygous Crx Knock-OUT or Knock-IN mice carrying the mutation E168d2 or R90W. Results provide important information about the retinal genes affected by mutations in the transcription factor Crx, which have been implicated in human retinopathies.

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL6887

12 Samples

Download data: TXT

(Submitter supplied) Leber congenital amaurosis (LCA) includes congenital or early-onset blinding diseases, characterized by vision loss together with nystagmus and nonrecordable electroretinogram (ERG). At least 19 genes are associated with LCA. While most LCA is recessive, mutations in the homeodomain transcription factor gene CRX lead to autosomal dominant LCA. The mechanism of CRX-LCA is not understood. Here, we report a new spontaneous mouse mutant carrying a frameshift mutation in Crx (CrxRip). more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11002

20 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL16791 GPL24676

43 Samples

Download data: H5

(Submitter supplied) 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. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

5 Samples

Download data: H5

(Submitter supplied) 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. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

38 Samples

Download data: TXT

(Submitter supplied) Background: Mutations in the cone-rod-homeobox protein CRX are typically associated with dominant blinding retinopathies with variable age of onset and severity. Five well-characterized mouse models carrying different Crx mutations show a wide range of disease phenotypes. To determine if the phenotype variability correlates with distinct changes in CRX target gene expression, we perform RNA-seq analyses on three of these models and compare the results with published data. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

30 Samples

Download data: TXT

(Submitter supplied) Dozens of mutations in the photoreceptor-specific transcription factor CRX are linked with different human blinding diseases that vary in their severity and age of onset. How these mutations in a single TF cause a range of pathological phenotypes is not understood. We deployed massively parallel reporter assays (MPRAs) in live mouse retina to directly measure changes to CRX cis-regulatory function caused by two disease-causing mutations, one in the DNA binding domain (p.R90W) and the other in the activation domain (p.E168d2).

Organism:

Mus musculus; synthetic construct

Type:

Other

Platforms:

GPL19057 GPL19424

38 Samples

Download data: TSV

(Submitter supplied) To comprehensively capture changes in retinal transcriptome for the LCA7 organoids compared to control, we performed single cell RNA-sequencing (scRNAseq) using the 10X Genomics platform. Retinal organoids at D150 of differentiation were dissociated for scRNAseq analysis. scRNAseq data revealed significant dysregulation of specific photoreceptor genes between control and LCA7 organoids, as well as mutation-specific differences in various genes, including CRX, RCVRN, ARR3, and AIPL1.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

3 Samples

Download data: TAR

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus; synthetic construct

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing; Other

Platforms:

GPL17769 GPL24247

68 Samples

Download data: BIGWIG, NARROWPEAK

(Submitter supplied) Homeodomain transcription factors (HD TFs) are instrumental to vertebrate development. Mutations in HD TFs have been linked to human diseases, but their pathogenic mechanisms remain elusive. Here we use Cone-Rod Homeobox (CRX) as a model to decipher the disease-causing mechanisms of two HD mutations, p.E80A and p.K88N, that produce severe dominant retinopathies. Through integrated analysis of molecular and functional evidence in vitro and in knock-in mouse models, we uncover two novel gain-of-function mechanisms: p.E80A increases transactivation of canonical CRX target genes in developing photoreceptors; p.K88N alters CRX DNA-binding specificity resulting in binding at ectopic sites and severe perturbation of CRX target gene expression. more...

Organism:

synthetic construct

Type:

Other

Platform:

GPL17769

16 Samples

Download data: TXT

(Submitter supplied) Homeodomain transcription factors (HD TFs) are instrumental to vertebrate development. Mutations in HD TFs have been linked to human diseases, but their pathogenic mechanisms remain elusive. Here we use Cone-Rod Homeobox (CRX) as a model to decipher the disease-causing mechanisms of two HD mutations, p.E80A and p.K88N, that produce severe dominant retinopathies. Through integrated analysis of molecular and functional evidence in vitro and in knock-in mouse models, we uncover two novel gain-of-function mechanisms: p.E80A increases transactivation of canonical CRX target genes in developing photoreceptors; p.K88N alters CRX DNA-binding specificity resulting in binding at ectopic sites and severe perturbation of CRX target gene expression. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL24247

16 Samples

Download data: BIGWIG, NARROWPEAK

(Submitter supplied) Homeodomain transcription factors (HD TFs) are instrumental to vertebrate development. Mutations in HD TFs have been linked to human diseases, but their pathogenic mechanisms remain elusive. Here we use Cone-Rod Homeobox (CRX) as a model to decipher the disease-causing mechanisms of two HD mutations, p.E80A and p.K88N, that produce severe dominant retinopathies. Through integrated analysis of molecular and functional evidence in vitro and in knock-in mouse models, we uncover two novel gain-of-function mechanisms: p.E80A increases transactivation of canonical CRX target genes in developing photoreceptors; p.K88N alters CRX DNA-binding specificity resulting in binding at ectopic sites and severe perturbation of CRX target gene expression. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

36 Samples

Download data: TXT

(Submitter supplied) CRX is a key transcript factor for photoreceptor development and homeostasis. We have characterized the CRX-dependent cis-regulatory network by ChIP-chip analysis of 2 month old BL/6 mouse retinas using Affymetrix Mouse Promoter 1.0 arrays

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by genome tiling array

Platform:

GPL5811

1 Sample

Download data: BED, CEL, TXT

(Submitter supplied) In order to define the genomic targets of Crx, we carried out Crx chromatin-immunoprecipitation followed by massively parallel sequencing (ChIP-seq) of eight-week-old mouse retinas using the Solexa platform. Sequence reads were mapped to the genome and 'peaks' were identified. These data were subjected to extensive bioinformatic analysis. In addition, selected peaks were experimentally tested for cis-regulatory activity by electroporation as promoter-reporter fusions into living mouse retinas. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL9185

7 Samples

Download data: BED

(Submitter supplied) We assessed how the effects of transcription factor binding sites (TFBSs) on the activity of a cis-regulatory sequence (CRS) depend on the local sequence context. We constructed a library of synthetic CRSs composed of TFBSs enriched in mouse photoreceptors and assayed them by massively parallel reporter assay in live mouse retina. We used the resulting data to train neural network-based models that predict CRS activity from sequence.

Organism:

synthetic construct; Mus musculus

Type:

Other

Platforms:

GPL19057 GPL19424

4 Samples

Download data: FA, TXT

(Submitter supplied) Many transcription factors regulating the production, survival and function of photoreceptor cells in the retina have been identified, but little is known about transcriptional co-regulators in retinal health and disease. Here we show that BCL6 co-repressor (BCOR), a polycomb repressive complex I factor mutated in various cancers, negatively regulates photoreceptor gene expression. Using proteomics and promoter assays, we find that BCOR interacts with the photoreceptor transcription factors OTX2 and CRX, and reduces their ability to activate the promoters of photoreceptor-specific genes, such as Rhodopsin and Nrl. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL24247 GPL17021

14 Samples

Download data: BED, BIGWIG, TXT, XLSX