ArticleDevelopmental biology2013
A distant, cis-acting enhancer drives induction of Arf by Tgfβ in the developing eye.
Article in Developmental biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Modeling complex age-related eye disease.Progress in retinal and eye research · 2024Review
- Long non-coding RNA APDC plays important regulatory roles in metabolism of bone and adipose tissues.RNA biology · 2023Article
- Methyltransferase Inhibition Enables TgfMolecular and cellular biology · 2023Article
- Review
- Exon skipping in genes encoding lineage-defining myogenic transcription factors in rhabdomyosarcoma.Cold Spring Harbor molecular case studies · 2022Article
- The Senescence Markers p16INK4A, p14ARF/p19ARF, and p21 in Organ Development and Homeostasis.Cells · 2022Review
- Transcriptional regulation of INK4/ARF locus by cis and trans mechanisms.Frontiers in cell and developmental biology · 2022Review
- Bayesian Modeling Identifies PLAG1 as a Key Regulator of Proliferation and Survival in Rhabdomyosarcoma Cells.Molecular cancer research : MCR · 2020Article
- Testis-specific Arf promoter expression in a transposase-aided BAC transgenic mouse model.Molecular biology reports · 2019Article
- Identification ofMolecular cancer research : MCR · 2019Article
- Mice Homozygous for a Deletion in the Glaucoma Susceptibility Locus INK4 Show Increased Vulnerability of Retinal Ganglion Cells to Elevated Intraocular Pressure.The American journal of pathology · 2016Article
- Functional genomics of the 9p21.3 locus for atherosclerosis: clarity or confusion?Current cardiology reports · 2014Review
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Authors and funding
5 authors.
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Abstract
The Arf tumor suppressor represents one of several genes encoded at the Cdkn2a and Cdkn2b loci in the mouse. Beyond its role blunting the growth of incipient cancer cells, the Arf gene also plays an essential role in development: its gene product, p19(Arf), is induced by Tgfβ2 in the developing eye to dampen proliferative signals from Pdgfrβ, which effect ultimately fosters the vascular remodeling required for normal vision in the mouse. Mechanisms underlying Arf induction by Tgfβ2 are not fully understood. Using the chr4(Δ70 kb/Δ70 kb) mouse, we now show that deletion of the coronary artery disease (CAD) risk interval lying upstream of the Cdkn2a/b locus represses developmentally-timed induction of Arf resulting in eye disease mimicking the persistent hyperplastic primary vitreous (PHPV) found in Arf-null mice and in children. Using mouse embryo fibroblasts, we demonstrate that Arf induction by Tgfβ is blocked in cis to the 70 kb deletion, but Arf induction by activated RAS and cell culture "shock" is not. Finally, we show that Arf induction by Tgfβ is derailed by preventing RNA polymerase II recruitment following Smad 2/3 binding to the promoter. These findings provide the first evidence that the CAD risk interval, located at a distance from Arf, acts as a cis enhancer of Tgfβ2-driven induction of Arf during development.
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