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Functional analysis of Vsx2 super-enhancer reveals an autoregulatory network governing Vsx2 expression during retinogenesis

ABSTRACT: Functional analysis of Vsx2 super-enhancer reveals an autoregulatory network governing Vsx2 expression during retinogenesis

PROVIDER: PRJNA803274 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17879925_1.fastq.gz	Fastqsanger.gz
	SRR17879925_2.fastq.gz	Fastqsanger.gz
	SRR17879926_1.fastq.gz	Fastqsanger.gz
	SRR17879926_2.fastq.gz	Fastqsanger.gz
	SRR17879927_1.fastq.gz	Fastqsanger.gz

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Functional analysis of Vsx2 super-enhancer reveals an autoregulatory network governing Vsx2 expression during retinogenesis [RNA-seq_mouse]

Project description:The roles of retinal cis-regulatory landscape in controlling the expression of gene regulatory networks important for retinogenesis remain poorly understood. Vsx2 is a transcription factor essential for retinal proliferation and bipolar cell differentiation but the molecular mechanisms underlying its developmental roles are unclear. Here, we profiled VSX2 genomic occupancy during mouse retinogenesis, revealing extensive retinal gene regulatory networks associated with Vsx2 during development. We defined an autoregulatory loop in which VSX2 binds and transactivates its own enhancer in association with the transcription factor PAX6 . The Vsx2 regulatory landscape contains elements that are required for Vsx2 expression, retinal proliferation and proper cell type differentiation. We further show that retinae in which the Vsx2 enhancer landscape has been largely deleted suffer a bias toward photoreceptor production. Genomic data indicate that VSX2 occupies cis-regulatory elements nearby genes associated with photoreceptor differentiation and homeostasis in mouse and human retinae, including a conserved region nearby the rod-specifying factor Prdm1. We provide evidence that VSX2 associates with OTX2 and can act to suppress OTX2-dependent enhancer transactivation of Prdm1 enhancer. Taken together, our analyses illuminate important mechanistic insights on how VSX2 is engaged with gene regulatory networks that are essential for retinal proliferation and cell fate acquisition.

2022-07-13 | GSE196104 | GEO

Functional analysis of Vsx2 super-enhancer reveals an autoregulatory network governing Vsx2 expression during retinogenesis [ChIP-seq_mouse]

2022-07-13 | GSE196103 | GEO

Functional analysis of Vsx2 super-enhancer reveals an autoregulatory network governing Vsx2 expression during retinogenesis [ChIP-seq_human]

2022-07-13 | GSE196097 | GEO

Functional analysis of Vsx2 super-enhancer reveals an autoregulatory network governing Vsx2 expression during retinogenesis [ChIP-seq_human]

Project description:Functional analysis of Vsx2 super-enhancer reveals an autoregulatory network governing Vsx2 expression during retinogenesis [ChIP-seq_human]

| PRJNA803241 | ENA

Functional analysis of Vsx2 super-enhancer reveals an autoregulatory network governing Vsx2 expression during retinogenesis [ChIP-seq_mouse]

Project description:Functional analysis of Vsx2 super-enhancer reveals an autoregulatory network governing Vsx2 expression during retinogenesis [ChIP-seq_mouse]

| PRJNA803304 | ENA

Functional analysis of Vsx2 super-enhancer reveals an autoregulatory network governing Vsx2 expression during retinogenesis [RNA-seq_mouse]

Project description:Functional analysis of Vsx2 super-enhancer reveals an autoregulatory network governing Vsx2 expression during retinogenesis [RNA-seq_mouse]

| PRJNA803305 | ENA

Functional analysis of Vsx2 super-enhancer reveals an autoregulatory network governing Vsx2 expression during retinogenesis

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-07-13 | GSE196106 | GEO

Vsx2 Super-Enhancer

Project description:Identification of a bifunctional super-enhancer in retinal development

| PRJEB43302 | ENA

Identification of a modular super-enhancer in murine retinal development

Project description:Single cell RNA-sequencing shows cell type specific expression of genes in the retina. Single cell ATAC-sequencing of the wild type retina at multiple stages revealed that chromatin in the Vsx2 CRC SE, a stage- and cell type-specific core regulatory circuit super-enhancer (CRC-SE) upstream of the Vsx2 gene, was only open in bipolar cells in Region3 in adult retina. Chromatin in Region0 was open in retinal progenitor cells in E14.5 retina.

2021-11-16 | GSE169262 | GEO

Identification of Evolutionarily Conserved VSX2 Enhancers in Retinal Development

Project description:Super-enhancers (SEs) are expansive regions of genomic DNA that regulate the expression of genes involved in cell identity and cell fate. Recently, we found that distinct modules within a murine SE regulate gene expression of transcription factor Vsx2 in a developmental stage- and cell-type specific manner. In the present study, we examine the ability of these modules to drive retinal development between species. By inserting the human build of one Vsx2 SE module into a mouse with microphthalmia, eye size was rescued. To understand the implications of these SE modules in a model of human development, we generated human retinal organoids. Deleting one module results in small organoids, recapitulating the small-eyed phenotype of mice with microphthalmia, while deletion of the other module leads to a complete loss of ON cone bipolar neurons. This prototypical SE serves as a model for uncoupling developmental stage- and cell-type specific effects of neurogenic transcription factors with complex expression patterns. Moreover, by elucidating the gene regulatory mechanisms, we can begin to examine how dysregulation of these mechanisms contributes to phenotypic diversity and disease.

2024-06-04 | GSE268990 | GEO

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