The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Controlling Long-Range Genomic Interactions at a Native Locus by Targeted Tethering of a Looping Factor
Open accessAbstract
Chromatin loops juxtapose distal enhancers with active promoters, but their molecular architecture and relationship with transcription remain unclear. In erythroid cells, the locus control region (LCR) and β-globin promoter form a chromatin loop that requires transcription factor GATA1 and the associated molecule Ldb1. We employed artificial zinc fingers (ZF) to tether Ldb1 to the β-globin promoter in GATA1 null erythroblasts, in which the β-globin locus is relaxed and inactive. Remarkably, targeting Ldb1 or only its self-association domain to the β-globin promoter substantially activated β-globin transcription in the absence of GATA1. Promoter-tethered Ldb1 interacted with endogenous Ldb1 complexes at the LCR to form a chromatin loop, causing recruitment and phosphorylation of RNA polymerase II. ZF-Ldb1 proteins were inactive at alleles lacking the LCR, demonstrating that their activities depend on long-range interactions. Our findings establish Ldb1 as a critical effector of GATA1-mediated loop formation and indicate that chromatin looping causally underlies gene regulation.
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“In contrast to YY1 and ZNF143, LDB1 has been shown to form loops independently of both cohesin and CTCF [371, 375].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [371]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“LDB1 was first identified as a looping factor in the mouse β-globin locus [317, 371].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [371]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“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 [88]
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In the citing paper
“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 [88]
In the citing paper
“and physical contact between enhancer-promoter pairs appears to be sufficient for gene activation.26”
From Recent evidence that TADs and chromatin loops are dynamic structures (2018) · cites this paper as [26]
In the citing paper
“Tethering the SA domain to the LCR (L-SA in Figure 1) or β-major promoter (Deng et al., 2012, and data not shown) did not activate βh1-globin expression”
From Reactivation of developmentally silenced globin genes by forced chromatin looping (2014) · cites this paper as Deng et al., 2012
In the citing paper
“In adult type murine erythroid cells, Ldb1 is required for the juxtaposition between the LCR and the adult β-major globin gene (Deng et al., 2012; Song et al., 2007).”
From Reactivation of developmentally silenced globin genes by forced chromatin looping (2014) · cites this paper as Deng et al., 2012
In the citing paper
“These results demonstrated that forced juxtaposition of an enhancer and promoter via chromatin looping can trigger gene activation”
From Reactivation of developmentally silenced globin genes by forced chromatin looping (2014) · cites this paper as Deng et al., 2012
In the citing paper
“Finally, previous 3C experiments demonstrated the sufficiency of tethered Ldb1 for full reconstitution of an LCR-β-globin promoter loop in immature adult erythroid cells in which the globin locus is otherwise unlooped (Deng et al., 2012).”
From Reactivation of developmentally silenced globin genes by forced chromatin looping (2014) · cites this paper as Deng et al., 2012
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Citations
Cites
Capturing Chromosome Conformation
Dekker, J., Rippe, K., Dekker, M., & Kleckner, N. (2002) · Science · doi:10.1126/science.1067799 · Cited by 3,652 · cited 2×
“The use of chromosome conformation capture (3C) and its derivatives has revealed that distant chromosomal elements can be juxtaposed to form chromatin loops, thus providing one mechanism of long-range enhancer function (Cullen et al., 1993; Dekker et al., 2002).”
Looping and Interaction between Hypersensitive Sites in the Active β-globin Locus
Tolhuis, B., Palstra, R.-J., Splinter, E., Grosveld, F., & de Laat, W. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00781-5 · Cited by 1,344 · cited 2×
“…arose from studies of the mammalian b-globin locus, which is among the first gene clusters at which long-range chromosomal interactions between a powerful distal enhancer, the locus control region (LCR), and the target b-globin promoters were described (Carter et al., 2002; Tolhuis et al., 2002).”
Pevny, L., Simon, M. C., Robertson, E., Klein, W. H., Tsai, S.-F., D'Agati, V., Orkin, S. H., & Costantini, F. (1991) · Nature · doi:10.1038/349257a0 · Cited by 1,308 · cited 1×
“GATA1 is a DNA-binding protein essential for normal erythroid differentiation and b-globin gene expression (Evans and Felsenfeld, 1989; Pevny et al., 1991; Tsai et al., 1989).”
Tsai, S., Martin, D. I. K., Zon, L. I., D’Andrea, A. D., Wong, G. G., & Orkin, S. H. (1989) · Nature · doi:10.1038/339446a0 · Cited by 884 · cited 1×
“GATA1 is a DNA-binding protein essential for normal erythroid differentiation and b-globin gene expression (Evans and Felsenfeld, 1989; Pevny et al., 1991; Tsai et al., 1989).”
The Discovery of Zinc Fingers and Their Applications in Gene Regulation and Genome Manipulation
Klug, A. (2010) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-010909-095056 · Cited by 710 · cited 3×
“ZFs have previously been linked to activation domains to successfully activate gene expression (Klug, 2010).”
InfluentialLong-range chromatin regulatory interactions in vivo
Carter, D., Chakalova, L., Osborne, C. S., Dai, Y.-F., & Fraser, P. (2002) · Nature Genetics · doi:10.1038/ng1051 · Cited by 663 · cited 3×
“Fundamental insights into these issues arose from studies of the mammalian b-globin locus, which is among the first gene clusters at which long-range chromosomal interactions between a powerful distal enhancer, the locus control region (LCR), and the target b-globin promoters were described (Carter et al., 2002; Tolhu…”
Transcriptional regulation of erythropoiesis: an affair involving multiple partners
Cantor, A. B., & Orkin, S. H. (2002) · Oncogene · doi:10.1038/sj.onc.1205326 · Cited by 610 · cited 1×
“However, physical interactions among all of these proteins have been reported (Cantor and Orkin, 2002), making it difficult to distinguish whether they function in linear or parallel pathways.”
The erythroid-specific transcription factor eryf1: A new finger protein
Evans, T., & Felsenfeld, G. (1989) · Cell · doi:10.1016/0092-8674(89)90940-9 · Cited by 580 · cited 1×
“GATA1 is a DNA-binding protein essential for normal erythroid differentiation and b-globin gene expression (Evans and Felsenfeld, 1989; Pevny et al., 1991; Tsai et al., 1989).”
The β-globin nuclear compartment in development and erythroid differentiation
Palstra, R.-J., Tolhuis, B., Splinter, E., Nijmeijer, R., Grosveld, F., & de Laat, W. (2003) · Nature Genetics · doi:10.1038/ng1244 · Cited by 559
Proximity among Distant Regulatory Elements at the β-Globin Locus Requires GATA-1 and FOG-1
Vakoc, C. R., Letting, D. L., Gheldof, N., Sawado, T., Bender, M. A., Groudine, M., Weiss, M. J., Dekker, J., & Blobel, G. A. (2005) · Molecular Cell · doi:10.1016/j.molcel.2004.12.028 · Cited by 490 · cited 6×
“Using HS2 as the anchor region, we found that, in parental G1E cells, the 3C signals generally declined with increasing distance (Figure 3A), which is consistent with our previous observations (Vakoc et al., 2005).”
Influential
Flagged first, then by citations
Research works printed but not linked: 1
- Tripic, T., Deng, W., Cheng, Y., Zhang, Y., Vakoc, C.R., Gregory, G.D., Hardison, R.C., and Blobel, G.A. (2009). SCL and associated proteins distinguish active from repressive GATA transcription factor complexes. Blood 113, 2191–2201. · DOI
Cited by
Sorted by citations
Organization and function of the 3D genome
Bonev, B., & Cavalli, G. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.112 · Cited by 1,174
Cas9 as a versatile tool for engineering biology
Mali, P., Esvelt, K. M., & Church, G. M. (2013) · Nature Methods · doi:10.1038/nmeth.2649 · Cited by 1,197
Long-range enhancer–promoter contacts in gene expression control
Schoenfelder, S., & Fraser, P. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0128-0 · Cited by 1,102
Exploring the three-dimensional organization of genomes: Interpreting chromatin interaction data
Dekker, J., Marti-Renom, M. A., & Mirny, L. A. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3454 · Cited by 1,068
“Further, the looping interaction directly stimulates transcription by facilitating recruitment and phosphorylation of RNA polymerase II 39 .”
BackgroundYY1 Is a Structural Regulator of Enhancer-Promoter Loops
Weintraub, A. S., Li, C. H., Zamudio, A. V., Sigova, A. A., Hannett, N. M., Day, D. S., Abraham, B. J., Cohen, M. A., Nabet, B., Buckley, D. L., et al. (2017) · Cell · doi:10.1016/j.cell.2017.11.008 · Cited by 992
“Nonetheless, most recent study of eukaryotic enhancer-promoter interactions has focused on cofactors that lack DNA binding capabilities and bridge enhancer-bound transcription factors and promoter-bound transcription apparatus (Allen and Taatjes, 2015; Deng et al., 2012; Jeronimo et al., 2016; Kagey et al., 2010; Mali…”
Metadata
- Authors
- Deng, W., Lee, J., Wang, H., Miller, J., Reik, A., Gregory, P. D., Dean, A., & Blobel, G. A.
- Affiliations
- Children's Hospital of Philadelphia (US)
- National Institutes of Health (US)
- Sangamo BioSciences (United States) (US)
- Corresponding author
- Blobel, Gerd A.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-06
- Volume
- 149
- Issue
- 6
- Pages
- 1233-1244
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3372860
- OpenAlex
- W1970831058
- Cited by
- 734
- References
- 49
- Citations by year
- 2026: 22 · 2025: 42 · 2024: 48 · 2023: 54 · 2022: 48 · 2021: 58 · 2020: 60 · 2019: 70 · 2018: 57 · 2017: 50 · 2016: 51 · 2015: 60 · 2014: 62 · 2013: 45 · 2012: 7
- FWCI
- 22.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL119479)
- National Institute of Diabetes and Digestive and Kidney Diseases (R37DK058044, R01DK054937)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Genetics (clinical) › Hemoglobinopathies and Related Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- chromatin looping, locus control region, beta-globin promoter, LDB1, GATA-1, erythroid cells, enhancer-promoter interactions, RNA polymerase II phosphorylation, transcriptional activation
- MeSH terms
- Animals, Cell Line, Cell Separation, Chromatin, DNA-Binding Proteins, Embryo, Mammalian, Erythroblasts, Female, Gene Expression Regulation, Male, Promoter Regions, Genetic, Transcription, Genetic, Zinc Fingers, Protein Structure, Tertiary, GATA1 Transcription Factor, Mice, beta-Globins, LIM Domain Proteins
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