A SOX2-VSX2 axis modulates a core cis-regulatory circuitry to safeguard retinal neural competence
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1181861 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Retinal neurogenesis is mediated by the coordinated activities of a complex gene regulatory network (GRN) of transcription factors (TFs) in multipotent retinal progenitor cells (RPCs). How this GRN mechanistically guides neural competence remains poorly understood. Here, we describe integrated transcriptional, genetic, and genomic analyses to identify the regulatory mechanisms of SOX2, a critical factor for RPC neural competency. We show that SOX2 is preferentially enriched in the RPC-specific enhancer landscape associated with essential regulators of retinogenesis. Perturbation of SOX2 expression leads to a failure in retinogenesis initiation as a result of selective loss of enhancer activity near key genes underlying proliferation and lineage specification. We identified the RPC transcription factor VSX2 as a binding partner for SOX2, and together they target a core retina-specific chromatin repertoire characterized by enhanced TF binding and robust chromatin accessibility. We delineate a SOX2-VSX2 common transcriptional code that promotes the expression of critical regulators of neurogenesis and suppresses the acquisition of alternative lineage cell fate. Our data illuminate fundamental biological insights on how transcription factors act in concert to drive chromatin-based genetic programs underlying retinal neural competence.
2025-06-23 | GSE281032 | GEO
Project description:Retinal neurogenesis is mediated by the coordinated activities of a complex gene regulatory network (GRN) of transcription factors (TFs) in multipotent retinal progenitor cells (RPCs). How this GRN mechanistically guides neural competence remains poorly understood. Here, we describe integrated transcriptional, genetic, and genomic analyses to identify the regulatory mechanisms of SOX2, a critical factor for RPC neural competency. We show that SOX2 is preferentially enriched in the RPC-specific enhancer landscape associated with essential regulators of retinogenesis. Perturbation of SOX2 expression leads to a failure in retinogenesis initiation as a result of selective loss of enhancer activity near key genes underlying proliferation and lineage specification. We identified the RPC transcription factor VSX2 as a binding partner for SOX2, and together they target a core retina-specific chromatin repertoire characterized by enhanced TF binding and robust chromatin accessibility. We delineate a SOX2-VSX2 common transcriptional code that promotes the expression of critical regulators of neurogenesis and suppresses the acquisition of alternative lineage cell fate. Our data illuminate fundamental biological insights on how transcription factors act in concert to drive chromatin-based genetic programs underlying retinal neural competence.
2025-06-23 | GSE281031 | GEO
Project description:Retinal neurogenesis is mediated by the coordinated activities of a complex gene regulatory network (GRN) of transcription factors (TFs) in multipotent retinal progenitor cells (RPCs). How this GRN mechanistically guides neural competence remains poorly understood. Here, we describe integrated transcriptional, genetic, and genomic analyses to identify the regulatory mechanisms of SOX2, a critical factor for RPC neural competency. We show that SOX2 is preferentially enriched in the RPC-specific enhancer landscape associated with essential regulators of retinogenesis. Perturbation of SOX2 expression leads to a failure in retinogenesis initiation as a result of selective loss of enhancer activity near key genes underlying proliferation and lineage specification. We identified the RPC transcription factor VSX2 as a binding partner for SOX2, and together they target a core retina-specific chromatin repertoire characterized by enhanced TF binding and robust chromatin accessibility. We delineate a SOX2-VSX2 common transcriptional code that promotes the expression of critical regulators of neurogenesis and suppresses the acquisition of alternative lineage cell fate. Our data illuminate fundamental biological insights on how transcription factors act in concert to drive chromatin-based genetic programs underlying retinal neural competence.
2025-06-23 | GSE281030 | GEO
Project description:A SOX2-VSX2 axis modulates a core cis-regulatory circuitry to safeguard retinal neural competence [ATAC-seq]
| PRJNA1181862 | ENA
Project description:A SOX2-VSX2 axis modulates a core cis-regulatory circuitry to safeguard retinal neural competence [RNA-seq]
| PRJNA1181863 | ENA
Project description:A SOX2-VSX2 axis modulates a core cis-regulatory circuitry to safeguard retinal neural competence [CUT&RUN]
| PRJNA1181864 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2025-06-23 | GSE281033 | GEO
Project description:Small distortions in transcriptional networks might lead to drastic phenotypical changes, especially in cellular developmental programs such as competence for natural transformation. Here, we report a pervasive circuitry rewiring for competence and predation interplay in commensal streptococci. Canonically, in model species of streptococci such as Streptococcus pneumoniae and Streptococcus mutans, the pheromone-based two-component system BlpRH is a central node that orchestrates the production of antimicrobial compounds (bacteriocins) and incorporates signal from the competence activation cascade. However, the human commensal Streptococcus salivarius does not contain a functional BlpRH pair and in this species, the competence signaling system ComRS directly couples bacteriocin production and competence commitment. This network shortcut might account for an optimal reaction against microbial competitors and could explain the high prevalence of S. salivarius in the human digestive tract. Moreover, the broad spectrum of bacteriocin activity against pathogenic bacteria showcases the commensal and genetically tractable S. salivarius species as a user-friendly model for natural transformation and bacterial predation.
2018-01-10 | GSE100416 | GEO
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 | GSE196097 | GEO
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