ArticleNucleic acids research2014
Dissecting the function of the adult β-globin downstream promoter region using an artificial zinc finger DNA-binding domain.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 13 citations in OpenAlex.
- Super-enhancer mediated regulation of adult β-globin gene expression: the role of eRNA and Integrator.Nucleic acids research · 2021Article
- Chromatin Manipulation and Editing: Challenges, New Technologies and Their Use in Plants.International journal of molecular sciences · 2021Review
- Phase Separation and Transcription Regulation: Are Super-Enhancers and Locus Control Regions Primary Sites of Transcription Complex Assembly?BioEssays : news and reviews in molecular, cellular and developmental biology · 2019Review
- Identification of a Novel Enhancer/Chromatin Opening Element Associated with High-Level γ-Globin Gene Expression.Molecular and cellular biology · 2018Article
- High Fractional Occupancy of a Tandem Maf Recognition Element and Its Role in Long-Range β-Globin Gene Regulation.Molecular and cellular biology · 2016Article
- Artificial zinc finger DNA binding domains: versatile tools for genome engineering and modulation of gene expression.Journal of cellular biochemistry · 2015Review
- Natural Remedies for the Treatment of Beta-Thalassemia and Sickle Cell Anemia-Current Status and Perspectives in Fetal Hemoglobin Reactivation.International scholarly research notices · 2014Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Developmental stage-specific expression of the β-type globin genes is regulated by many cis- and trans-acting components. The adult β-globin gene contains an E-box located 60 bp downstream of the transcription start site that has been shown to bind transcription factor upstream stimulatory factor (USF) and to contribute to efficient in vitro transcription. We expressed an artificial zinc finger DNA-binding domain (ZF-DBD) targeting this site (+60 ZF-DBD) in murine erythroleukemia cells. Expression of the +60 ZF-DBD reduced the recruitment and elongation of RNA polymerase II (Pol II) at the adult β-globin gene and at the same time increased the binding of Pol II at locus control region (LCR) element HS2, suggesting that Pol II is transferred from the LCR to the globin gene promoters. Expression of the +60 ZF-DBD also reduced the frequency of interactions between the LCR and the adult β-globin promoter. ChIP-exonuclease-sequencing revealed that the +60ZF-DBD was targeted to the adult β-globin downstream promoter and that the binding of the ZF-DBD caused alterations in the association of USF2 containing protein complexes. The data demonstrate that targeting a ZF-DBD to the adult β-globin downstream promoter region interferes with the LCR-mediated recruitment and activity of Pol II.
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Registered trials
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