Evidence map›Paper›PMID 41159420›Full record

ArticleDevelopment (Cambridge, England)2024

SOX2-driven enhancer landscape defines the transcriptional architecture of retinogenesis.

Fuyun Bian, Kimiasadat Golestaneh, Emily Davis, Abdullah Khan, Brendan Nicholson, Marwa Daghsni, Keevon Flohr, Silvia Liu, Susana da Silva, Len Pennacchio and 1 more

Abstract read
In one paragraph

Article in Development (Cambridge, England), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Fuyun BianDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.
Kimiasadat GolestanehDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.
Emily DavisDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.
Abdullah KhanDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.
Brendan NicholsonDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.
Marwa DaghsniDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.
Keevon FlohrDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.
Silvia LiuDepartment of Pharmacology and Chemical Biology and Drug Discovery Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Susana da SilvaDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.
Len PennacchioEnvironmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Issam AldiriDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.ORCID 0000-0002-0813-2943

Funding

Generation of an In Vivo Human Genome Transcriptional Enhancer DatasetR01HG003988 · NHGRI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI Len Alexander Pennacchio · 2006 to 2026
$24.1M
Virus Production and Manipulation of Protein/Gene Expression ModuleP30EY008098 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Yuanyuan Chen · 1989 to 2026
$17.8M
Role of retinoic acid signaling in fovea developmentR01EY033385 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Susana Isabel M M A da Silva · 2022 to 2026
$2.0M
Epigenetic basis of retinal cell fate determinationR01EY030861 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI AL DIRI, ISSAM · 2020 to 2024
$1.9M
Wiring and rewiring of the chromatin landscape during retinogenesisR01EY035619 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Issam Al Diri · 2024 to 2026
$1.2M
Eye and Ear Foundation of PittsburghNEI NIH HHS EY030861NEI NIH HHS EY035619NEI NIH HHS P30 EY008098NEI NIH HHS R01 EY030861NEI NIH HHS R01 EY033385NEI NIH HHS R01 EY035619NHGRI NIH HHS R01 HG003988NHGRI NIH HHS R01HG003988NIH HHS DE-AC02-05CH11231NIH HHS EY030861NIH HHS EY035619NIH HHS EY08098NIH HHS R01HG003988Research to Prevent BlindnessUniversity of CaliforniaUniversity of Pittsburgh
6 · The paper itself

Abstract

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. In this study, we present integrated transcriptional, genetic and genomic analyses to uncover the regulatory mechanisms of SOX2, a key factor in establishing neural identity in RPCs. We show that SOX2 is preferentially enriched in the RPC-specific enhancer landscape associated with essential regulators of retinogenesis. Disruption of SOX2 expression impairs retinogenesis, marked by a selective loss of enhancer activity near genes essential for RPC proliferation and lineage specification. We identified the RPC transcription factor VSX2 as a binding partner for SOX2 and, together, SOX2 and VSX2 co-target a core, retina-specific chromatin repertoire characterized by enhanced TF binding and robust chromatin accessibility. This cooperative binding establishes a shared SOX2-VSX2 transcriptional code that promotes the expression of crucial regulators of neurogenesis while repressing 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 identity.

Indexed as

Enhancer Elements, GeneticNeurogenesisOrganogenesisRetinaSOXB1 Transcription FactorsTranscription, GeneticAnimalsCell LineageChromatinEye ProteinsGene Expression Regulation, DevelopmentalGene Regulatory NetworksHomeodomain ProteinsMiceTranscription FactorsChromatinEye ProteinsHomeodomain ProteinsSox2 protein, mouseSOXB1 Transcription FactorsTranscription FactorsVsx2 protein, mouseChromatinEnhancersMouseNeurogenesisPioneer factorRetinaTranscription

Identifiers

PMID41159420
PMCPMC12687333

What Socratic holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.