Lamin A upregulation reorganizes the genome during rod photoreceptor degeneration
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ABSTRACT:
PROVIDER: PRJNA1003849 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25585515_1.fastq.gz | Fastqsanger.gz | |||
| SRR25585515_2.fastq.gz | Fastqsanger.gz | |||
| SRR25585516_1.fastq.gz | Fastqsanger.gz | |||
| SRR25585516_2.fastq.gz | Fastqsanger.gz | |||
| SRR25585517_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Lamin A upregulation reorganizes the genome during rod photoreceptor degeneration
| PRJNA1003125 | ENA
Project description:Neurodegenerative diseases are accompanied by dynamic changes in gene expression, including the upregulation of hallmark stress-responsive genes. While the transcriptional pathways that impart adaptive and maladaptive gene expression signatures have been the focus of intense study, the role of higher order nuclear organization in this process is less clear. Here, we examine the role of the nuclear lamina in genome organization during the degeneration of rod photoreceptors. Two proteins had previously been shown to be necessary and sufficient to tether heterochromatin at the nuclear envelope. The lamin B receptor (Lbr) is expressed during development, but downregulates upon rod differentiation. A second tether is the intermediate filament lamin A (LA), which is not normally expressed in murine rods. Here, we show that in the rd1 model of retinitis pigmentosa, LA ectopically upregulates in rod photoreceptors at the onset of degeneration. LA upregulation correlated with increased heterochromatin tethering at the nuclear periphery in rd1 rods, suggesting that LA reorganizes the nucleus. To determine how heterochromatin tethering affects the genome, we used in vivo electroporation to misexpress LA or Lbr in mature rods in the absence of degeneration, resulting in the restoration of conventional nuclear architecture. Using scRNA-seq, we show that reorganizing the nucleus via LA/Lbr misexpression has relatively minor effects on rod gene expression. Next, using ATAC-seq, we show that LA and Lbr both lead to marked increases in genome accessibility. Novel ATAC-seq peaks tended to be associated with stress-responsive genes. Together, our data reveal that heterochromatin tethers have a global effect on genome accessibility, and suggest that heterochromatin tethering primes the photoreceptor genome to respond to stress.
2023-11-02 | GSE240312 | GEO
Project description:Two proteins have previously been shown to be necessary and sufficient to tether heterochromatin at the nuclear envelope. The lamin B receptor (Lbr) is expressed during development, but downregulates upon rod differentiation. A second tether is the intermediate filament lamin A (LA), which is not normally expressed in murine rods.To determine how heterochromatin tethering affects the genome, we used in vivo electroporation to misexpress LA or Lbr in mature rods in the absence of degeneration, resulting in the restoration of conventional nuclear architecture. Using scRNA-seq, we show that reorganizing the nucleus via LA/Lbr misexpression has only minor effects on rod gene expression. Next, using ATAC-seq, we show that LA and Lbr similarly increase genome accessibility. Novel ATAC-seq peaks tended to distal to genes, but some peaks were associated with stress-responsive genes. Together, our data reveal that heterochromatin tethers have a global effect on genome accessibility, and suggest that LA –dependent genome reconfiguration might contribute to the stress response of rod photoreceptors.
2023-10-12 | GSE240465 | GEO
Project description:Neurodegenerative diseases are accompanied by dynamic changes in gene expression, including the upregulation of hallmark stress-responsive genes. While the transcriptional pathways that impart adaptive and maladaptive gene expression signatures have been the focus of intense study, the role of higher order nuclear organization in this process is less clear. Here, we examine the role of the nuclear lamina in genome organization during the degeneration of rod photoreceptors. Two proteins had previously been shown to be necessary and sufficient to tether heterochromatin at the nuclear envelope. The lamin B receptor (Lbr) is expressed during development, but downregulates upon rod differentiation. A second tether is the intermediate filament lamin A (LA), which is not normally expressed in murine rods. Here, we show that in the rd1 model of retinitis pigmentosa, LA ectopically upregulates in rod photoreceptors at the onset of degeneration. LA upregulation correlated with increased heterochromatin tethering at the nuclear periphery in rd1 rods, suggesting that LA reorganizes the nucleus. To determine how heterochromatin tethering affects the genome, we used in vivo electroporation to misexpress LA or Lbr in mature rods in the absence of degeneration, resulting in the restoration of conventional nuclear architecture. Using scRNA-seq, we show that reorganizing the nucleus via LA/Lbr misexpression has relatively minor effects on rod gene expression. Next, using ATAC-seq, we show that LA and Lbr both lead to marked increases in genome accessibility. Novel ATAC-seq peaks tended to be associated with stress-responsive genes. Together, our data reveal that heterochromatin tethers have a global effect on genome accessibility, and suggest that heterochromatin tethering primes the photoreceptor genome to respond to stress.
| S-EPMC10600220 | biostudies-literature
Project description:Mutation of rod photoreceptor-enriched transcription factors is a major cause of inherited blindness. We identified the orphan nuclear hormone receptor ERRβ as selectively expressed in rod photoreceptors. Overexpression of ERRβ induces expression of rod-specific genes in retinas of both wildtype and in Nrl-/- mice, which lack rod photoreceptors. Mutation of ERRβ results in dysfunction and degeneration of rods, while inverse agonists of ERRβ trigger rapid rod degeneration, which is rescued by constitutively active mutants of ERRβ. ERRβ coordinates expression of multiple genes that are rate-limiting regulators of ATP generation and consumption in photoreceptors. Furthermore, enhancing ERRβ activity rescues photoreceptor defects that result from loss of the photoreceptor-specific transcription factor Crx. Our findings demonstrate that ERRβ is a critical regulator of rod photoreceptor function and survival, and suggest that ERRβ agonists may be useful in the treatment of certain retinal dystrophies. Affymetrix MOE430 microarrays were used to analyze the expression patterns of P21 mouse retinal tissues. The results were compared across the variable of Genotype, specifically ERRβ knockout versus wildtype.
2010-07-30 | E-GEOD-21944 | biostudies-arrayexpress
Project description:Mutation of rod photoreceptor-enriched transcription factors is a major cause of inherited blindness. We identified the orphan nuclear hormone receptor ERRβ as selectively expressed in rod photoreceptors. Overexpression of ERRβ induces expression of rod-specific genes in retinas of both wildtype and in Nrl-/- mice, which lack rod photoreceptors. Mutation of ERRβ results in dysfunction and degeneration of rods, while inverse agonists of ERRβ trigger rapid rod degeneration, which is rescued by constitutively active mutants of ERRβ. ERRβ coordinates expression of multiple genes that are rate-limiting regulators of ATP generation and consumption in photoreceptors. Furthermore, enhancing ERRβ activity rescues photoreceptor defects that result from loss of the photoreceptor-specific transcription factor Crx. Our findings demonstrate that ERRβ is a critical regulator of rod photoreceptor function and survival, and suggest that ERRβ agonists may be useful in the treatment of certain retinal dystrophies.
2010-07-02 | GSE21944 | GEO
Project description:Mouse rod photoreceptors isolated from retinas of Prkaa2 rod photoreceptor specific knockout mice were processed for phosphoproteomics to elucidate downstream kinase targets. Prkaa2 is an isoform of the catalytic subunit of AMP-activated protein kinase (AMPK), an essential nutrient-sensing enzyme responsible for maintaining many metabolic processes.
2024-06-16 | PXD045669 | Pride
Project description:Mouse rod photoreceptor specific Prkaa1 knockouts were isolated from retinas and processed for phosphoproteomics to elucidate downstream kinase targets. Prkaa1 is one of the isoforms for the catalytic subunit of AMP-activated protein kinase (AMPK), an essential nutrient sensing enzyme responsible for maintaining many metabolic processes.
2024-06-16 | PXD045667 | Pride
Project description:Retinitis pigmentosa is an inherited disease with sequential retinal degeneration of rod then cone photoreceptors leading to blindness. As in this human syndrome the rd1 mouse model carries a recessive mutation in the rod-specific cGMP phosphodiesterase beta subunit gene leading to rod followed by cone photoreceptor death. The cascade of early events leading to the induction of rod cell death through apoptosis remains unknown. We report a differential whole-genome expression profiling analysis of the wild-type and rd1 mouse retinal transcriptional program using high-density oligonucleotide microarrays with a time series experiment spanning the entire rod photoreceptor degeneration process. Among the 1252 genes found to be significantly differentially expressed, a key group of 19 loci showed distinct differences in expression early in development, suggesting that these genes of clinical interest may play a fundamental role in the induction of the rod photoreceptor degeneration.
2020-09-25 | GSE62020 | GEO
Project description:For isolation of rod, cone, and pineal photoreceptor cells, we used the transgenic zebrafish lines, Tg(rho:egfp)ja2Tg, Tg(gnat2:egfp)ja23Tg, and Tg(exorh:EGFP)ja1Tg, which express EGFP in rods, all cone subtypes, and pineal rod cells, respectively. Retinas were dissected from dark-adapted adult fish under dim red light. The isolated retinas were digested with trypsin in Ca2+-free Ringer’s solution. The reaction was terminated by adding soybean trypsin inhibitor and fetal bovine serum. The dissociated EGFP-positive cells were isolated with a fluorescence activating cell sorter (FACSAria, BD Biosciences) by the following three parameters: forward scatter, side scatter and green fluorescence. Goal was to determine differentially expressed genes among three types of photoreceptor cells.
2021-10-06 | GSE168749 | GEO