Forced chromatin looping raises fetal hemoglobin in adult sickle cells to higher levels than pharmacologic inducers
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Key Points: Ldb1 transcription factor self-association domain fused to γ-globin promoter-specific ZF protein increases HbF, reduces HbS in hSCD cells. In vitro reactivation of HbF mediated by ZF-Ldb1 exceeds pharmacologic treatment in adult hSCD cells.
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The functional significance of the physical approximation of the promoter to the enhancer was demonstrated in experiments on the activation of transcription through the forced formation of enhancer-promoter loops.
“The functional significance of the physical approximation of the promoter to the enhancer was demonstrated in experiments on the activation of transcription through the forced formation of enhancer-promoter loops [87,88].”
From Enhancer Function in the 3D Genome (2023) · cites this paper as [87]
Stimulation of promoter activity by forced looping with an enhancer is a strong argument in favor of the loop model.
“Stimulation of promoter activity by forced looping with an enhancer is a strong argument in favor of this model [87,88,110,111].”
From Enhancer Function in the 3D Genome (2023) · cites this paper as [87]
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- PHARMACOLOGIC AND ZF-Ldb1 INDUCTION OF HbF 1143 For personal use only. on January 29, 2019. by guest www.bloodjournal.org From online July 12, 2016 originally published doi:10.1182/blood-2016-01-691089 2016 128: 1139-1143 · DOI
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- Authors
- Breda, L., Motta, I., Lourenco, S., Gemmo, C., Deng, W., Rupon, J. W., Abdulmalik, O. Y., Manwani, D., Blobel, G. A., & Rivella, S.
- Affiliations
- Children's Hospital of Philadelphia (US)
- University of Milan (IT)
- Department of Pediatrics, Division of Hematology-Oncology, Children’s Blood and Cancer Foundation Laboratories, Weill Cornell Medical College, New York, NY;
- Weill Cornell Medicine (US)
- Howard Hughes Medical Institute (US)
- Albert Einstein College of Medicine (US)
- Corresponding author
- Blobel, Gerd A.
- Rivella, Stefano
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2016-08-25
- Volume
- 128
- Issue
- 8
- Pages
- 1139-1143
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC5000846
- OpenAlex
- W2465447473
- Cited by
- 83
- References
- 27
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 6 · 2023: 6 · 2022: 4 · 2021: 9 · 2020: 10 · 2019: 9 · 2018: 12 · 2017: 17 · 2016: 1 · 2015: 1
- FWCI
- 9.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- Funders
- Children's Hospital of Philadelphia
- National Institutes of Health (KL2TR000458)
- National Heart, Lung, and Blood Institute (K01HL103186, R01HL102449, R01HL119479)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK084188)
- National Center for Advancing Translational Sciences
- FP7 Health
- Topics
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Keywords
- sickle cell disease, fetal hemoglobin reactivation, chromatin looping, locus control region, LDB1, zinc finger proteins, decitabine, pomalidomide, hydroxyurea, tranylcypromine, butyrate, hemoglobin S, erythroid cells, lentiviral transduction
- MeSH terms
- Adult, Anemia, Sickle Cell, Chromatin, DNA-Binding Proteins, Fetal Hemoglobin, Hemoglobin, Sickle, Humans, Transcription Factors, Zinc Fingers, Antigens, CD34, Erythroid Cells, LIM Domain Proteins
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