ArticlePLoS genetics2011
Study of FoxA pioneer factor at silent genes reveals Rfx-repressed enhancer at Cdx2 and a potential indicator of esophageal adenocarcinoma development.
Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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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.
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Who cites it
44 citing papers in PubMed, 66 citations in OpenAlex.
- A retinoic acid-Rfx6 cascade modulates Wnt/Bmp-dependent gut tube patterning: insight into the molecular basis of Mitchell-Riley Syndrome.Development (Cambridge, England) · 2026Article
- A dual enhancer-attenuator element ensures transient Cdx2 expression during mouse posterior body formation.Developmental cell · 2025Article
- Primitive Hepatoblasts Driving Early Liver Development.bioRxiv : the preprint server for biology · 2025Article
- The yin and yang of pioneer transcription factors: Dual roles in repression and activation.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024Article
- The enhancer RNA, AANCR, regulates APOE expression in astrocytes and microglia.Nucleic acids research · 2024Article
- Pioneer and PRDM transcription factors coordinate bivalent epigenetic states to safeguard cell fate.Molecular cell · 2024Article
- Different chromatin-scanning modes lead to targeting of compacted chromatin by pioneer factors FOXA1 and SOX2.Cell reports · 2023Article
- TFAP2 paralogs facilitate chromatin access for MITF at pigmentation and cell proliferation genes.PLoS genetics · 2022Article
- Transcription factor-mediated intestinal metaplasia and the role of a shadow enhancer.Genes & development · 2022Article
- FoXA2 promotes esophageal squamous cell carcinoma progression by ZEB2 activation.World journal of surgical oncology · 2021Article
- RFX1: a promising therapeutic arsenal against cancer.Cancer cell international · 2021Review
- Enhancer redundancy in development and disease.Nature reviews. Genetics · 2021Review
- TET1 and 5-Hydroxymethylation Preserve the Stem Cell State of Mouse Trophoblast.Stem cell reports · 2020Article
- Pioneer Transcription Factors Initiating Gene Network Changes.Annual review of genetics · 2020Review
- Gene network transitions in embryos depend upon interactions between a pioneer transcription factor and core histones.Nature genetics · 2020Article
- cis Elements that Mediate RNA Polymerase II Pausing Regulate Human Gene Expression.American journal of human genetics · 2019Article
- TCam-2 Cells Deficient for SOX2 and FOXA2 Are Blocked in Differentiation and Maintain a Seminoma-Like Cell Fate In Vivo.Cancers · 2019Article
- Upregulated forkhead-box A3 elevates the expression of forkhead-box A1 and forkhead-box A2 to promote metastasis in esophageal cancer.Oncology letters · 2019Article
- Regulatory Factor X1 Downregulation Contributes to Monocyte Chemoattractant Protein-1 Overexpression in CD14+ MonocytesFrontiers in genetics · 2019Article
- Direct Neuronal Reprogramming Reveals Unknown Functions for Known Transcription Factors.Frontiers in neuroscience · 2019Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Understanding how silent genes can be competent for activation provides insight into development as well as cellular reprogramming and pathogenesis. We performed genomic location analysis of the pioneer transcription factor FoxA in the adult mouse liver and found that about one-third of the FoxA bound sites are near silent genes, including genes without detectable RNA polymerase II. Virtually all of the FoxA-bound silent sites are within conserved sequences, suggesting possible function. Such sites are enriched in motifs for transcriptional repressors, including for Rfx1 and type II nuclear hormone receptors. We found one such target site at a cryptic "shadow" enhancer 7 kilobases (kb) downstream of the Cdx2 gene, where Rfx1 restricts transcriptional activation by FoxA. The Cdx2 shadow enhancer exhibits a subset of regulatory properties of the upstream Cdx2 promoter region. While Cdx2 is ectopically induced in the early metaplastic condition of Barrett's esophagus, its expression is not necessarily present in progressive Barrett's with dysplasia or adenocarcinoma. By contrast, we find that Rfx1 expression in the esophageal epithelium becomes gradually extinguished during progression to cancer, i.e, expression of Rfx1 decreased markedly in dysplasia and adenocarcinoma. We propose that this decreased expression of Rfx1 could be an indicator of progression from Barrett's esophagus to adenocarcinoma and that similar analyses of other transcription factors bound to silent genes can reveal unanticipated regulatory insights into oncogenic progression and cellular reprogramming.
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Registered trials
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