Proximity among Distant Regulatory Elements at the β-Globin Locus Requires GATA-1 and FOG-1
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Recent evidence suggests that long-range enhancers and gene promoters are in close proximity, which might reflect the formation of chromatin loops. Here, we examined the mechanism for DNA looping at the beta-globin locus. By using chromosome conformation capture (3C), we show that the hematopoietic transcription factor GATA-1 and its cofactor FOG-1 are required for the physical interaction between the beta-globin locus control region (LCR) and the beta-major globin promoter. Kinetic studies reveal that GATA-1-induced loop formation correlates with the onset of beta-globin transcription and occurs independently of new protein synthesis. GATA-1 occupies the beta-major globin promoter normally in fetal liver erythroblasts from mice lacking the LCR, suggesting that GATA-1 binding to the promoter and LCR are independent events that occur prior to loop formation. Together, these data demonstrate that GATA-1 and FOG-1 are essential anchors for a tissue-specific chromatin loop, providing general insights into long-range enhancer function.
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Several TFs were required for looping between the LCR and the distal genes, including GATA-1, FOG-1, EKLF and NLI/Ldb1.
“Following the discovery of chromatin looping in the β-globin locus, it was ascertained that several TFs were required for looping between the LCR and the distal genes, including GATA-1, FOG-1, EKLF and NLI/Ldb1 [315–317].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [315]
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- Authors
- Vakoc, C. R., Letting, D. L., Gheldof, N., Sawado, T., Bender, M. A., Groudine, M., Weiss, M. J., Dekker, J., & Blobel, G. A.
- Affiliations
- Children's Hospital of Philadelphia (US)
- University of Massachusetts Chan Medical School (US)
- University of Washington (US)
- Corresponding author
- Blobel, Gerd A.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2005-02
- Volume
- 17
- Issue
- 3
- Pages
- 453-462
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2019666363
- Cited by
- 490
- References
- 5
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 9 · 2023: 10 · 2022: 8 · 2021: 15 · 2020: 12 · 2019: 14 · 2018: 15 · 2017: 21 · 2016: 23 · 2015: 26 · 2014: 25 · 2013: 37 · 2012: 33
- FWCI
- 15.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- eScholarship@UMassChan (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL65440, R01HL065440, T32 HL07439-26)
- National Human Genome Research Institute (HG 03143, R01HG003143)
- National Institute of General Medical Sciences (T32GM008216)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK58044, DK 44746, DK54937, R01DK054937)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Keywords
- GATA-1, FOG-1, beta-globin locus control region, long-range enhancers, chromatin looping, beta-globin promoter, hematopoietic transcription factors, enhancer-promoter interactions, tissue-specific gene regulation, transcriptional activation
- MeSH terms
- Animals, Base Sequence, Binding Sites, Carrier Proteins, Cell Line, DNA, DNA-Binding Proteins, Enhancer Elements, Genetic, Genes, Regulator, Globins, Humans, Mice, Mutant Strains, Nuclear Proteins, Nucleic Acid Conformation, Promoter Regions, Genetic, Protein Binding, RNA Polymerase II, Transcription Factors, Locus Control Region, Erythroid-Specific DNA-Binding Factors, GATA1 Transcription Factor, Mice
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