Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The Atoh7 shadow enhancer provides transcriptional robustness during retinal ganglion cell development

ABSTRACT: The Atoh7 shadow enhancer provides transcriptional robustness during retinal ganglion cell development

PROVIDER: PRJNA612318 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR11297425_1.fastq.gz	Fastqsanger.gz
	SRR11297425_2.fastq.gz	Fastqsanger.gz
	SRR11297426_1.fastq.gz	Fastqsanger.gz
	SRR11297426_2.fastq.gz	Fastqsanger.gz
	SRR11297427_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 12

Similar Datasets

The Atoh7 shadow enhancer provides transcriptional robustness during retinal ganglion cell development

Project description:The retinal ganglion cell (RGC) competence factor ATOH7 is dynamically expressed during retinal histogenesis. ATOH7 transcription is controlled by a promoter-adjacent primary enhancer and a remote shadow enhancer (SE). Deletion of the ATOH7 human SE causes non‑syndromic congenital retinal non-attachment (NCRNA) disease, characterized by optic nerve aplasia and total blindness. We used genome editing to model NCRNA in mice. Deletion of the murine SE reduces Atoh7 mRNA >5-fold, but does not recapitulate optic nerve loss; however, SEdel/KO (knockout) trans heterozygotes have thin optic nerves. By analyzing Atoh7 mRNA and protein levels, RGC development and survival, and chromatin landscape effects, we show how the SE ensures robust Atoh7 transcriptional output. Combining SE deletion, KO and wild-type alleles in a genotypic series, we determined the amount of Atoh7 needed to produce a normal complement of adult RGCs, and the secondary consequences of graded reductions in Atoh7 dosage. Together these data reveal the workings of an evolutionary fail-safe, a duplicate enhancer mechanism hard-wired in the machinery of vertebrate retinal ganglion cell genesis.

2020-08-25 | GSE146897 | GEO

Atoh7-independent specification of retinal ganglion cell identity

Project description:Atoh7-independent specification of retinal ganglion cell identity

| PRJNA658977 | ENA

Single cell transcriptomics reveals lineage trajectory of the retinal ganglion cells in wild-type and Atoh7-null retinas

Project description:Single cell transcriptomics reveals lineage trajectory of the retinal ganglion cells in wild-type and Atoh7-null retinas

2020-11-24 | GSE149040 | GEO

Atoh7-independent specification of retinal ganglion cell identity

Project description:Atoh7 Cut&Run on the developing mouse retina

2021-03-29 | GSE156756 | GEO

The <i>Atoh7</i> remote enhancer provides transcriptional robustness during retinal ganglion cell development.

Project description:The retinal ganglion cell (RGC) competence factor ATOH7 is dynamically expressed during retinal histogenesis. ATOH7 transcription is controlled by a promoter-adjacent primary enhancer and a remote shadow enhancer (SE). Deletion of the ATOH7 human SE causes nonsyndromic congenital retinal nonattachment (NCRNA) disease, characterized by optic nerve aplasia and total blindness. We used genome editing to model NCRNA in mice. Deletion of the murine SE reduces Atoh7 messenger RNA (mRNA) fivefold but does not recapitulate optic nerve loss; however, SEdel/knockout (KO) trans heterozygotes have thin optic nerves. By analyzing Atoh7 mRNA and protein levels, RGC development and survival, and chromatin landscape effects, we show that the SE ensures robust Atoh7 transcriptional output. Combining SE deletion and KO and wild-type alleles in a genotypic series, we determined the amount of Atoh7 needed to produce a normal complement of adult RGCs, and the secondary consequences of graded reductions in Atoh7 dosage. Together, these data reveal the workings of an evolutionary fail-safe, a duplicate enhancer mechanism that is hard-wired in the machinery of vertebrate retinal ganglion cell genesis.

| S-EPMC7474671 | biostudies-literature

A cis-regulatory module underlies retinal ganglion cell genesis and axonogenesis [Set2.Bulk RNA-Seq retina E14.5 WT and Atoh7 Large Enhancer KO]

Project description:During retinogenesis, the proneural bHLH transcription factor Atoh7 is transiently expressed in retinal progenitor cells (RPCs) and is required for retinal ganglion cell (RGC) differentiation. In humans, a deletion in a distal non-coding regulatory region upstream of ATOH7 is associated with nonsyndromic congenital retinal nonattachment (NCRNA) disorder, characterized by optic nerve atrophy and complete blindness. Here we functionally interrogate the significance of the Atoh7 enhancer landscape to retinogenesis. We demonstrate that deletion of the enhancer structure upstream of Atoh7 in mice leads to RGC deficiency, optic nerve hypoplasia and blood vascular abnormalities, phenocopying inactivation of Atoh7 and recapitulating key features of NCRNA. We further provide evidence that the loss of the Atoh7 remote enhancer impacts ipsilaterally-projecting RGCs and disrupts proper axonal projections to the brain targets. Transcriptionally, deletion of the Atoh7 remote enhancer is associated with dysregulation of axonogenesis genes, including the derepression of the axon repulsive cue Robo3 which is normally epigenetically silenced in the developing retina. Our data provide novel insights into how Atoh7 enhancer elements function to promote RGC development and optic nerve formation and uncover a key role of Atoh7 in the transcriptional control of axon guidance molecules possibly via epigenetic mechanisms.

2024-06-06 | GSE245540 | GEO

A cis-regulatory module underlies retinal ganglion cell genesis and axonogenesis [Set3.Bulk RNA-Seq retina E14.5 WT and Atoh7 Remote Enhancer KO]

2024-06-06 | GSE245541 | GEO

A cis-regulatory module underlies retinal ganglion cell genesis and axonogenesis [Set7.Bulk RNA-Seq P18 Cerebellum WT and Atoh7 Large Enhancer KO]

2024-06-06 | GSE245546 | GEO

A cis-regulatory module underlies retinal ganglion cell genesis and axonogenesis [Set5.H3K27me3 ChIP-Seq retina E14.5 WT and Atoh7 Remote enhancer KO]

2024-06-06 | GSE245543 | GEO

A cis-regulatory module underlies retinal ganglion cell genesis and axonogenesis [Set8.Bulk RNA-Seq P18 Cerebellum WT and Atoh7 remote Enhancer KO]

2024-06-06 | GSE245547 | GEO