ArticleMolecular and cellular biology2001
Sequences flanking hypersensitive sites of the beta-globin locus control region are required for synergistic enhancement.
Article in Molecular and cellular biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 48 citations in OpenAlex.
- Mechanisms of Globin Gene Regulation in Mammals.Annual review of genetics · 2025Review
- DNA G-quadruplex structures act as functional elements in α- and β-globin enhancers.Genome biology · 2025Article
- Creating New β-Globin-Expressing Lentiviral Vectors by High-Resolution Mapping of Locus Control Region Enhancer Sequences.Molecular therapy. Methods & clinical development · 2020Article
- Engineering Globin Gene Expression.Molecular therapy. Methods & clinical development · 2019Review
- An Optimized Lentiviral Vector Efficiently Corrects the Human Sickle Cell Disease Phenotype.Molecular therapy. Methods & clinical development · 2018Article
- Identifying and mapping cell-type-specific chromatin programming of gene expression.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Evolution of hemoglobin and its genes.Cold Spring Harbor perspectives in medicine · 2012Article
- MBD2 contributes to developmental silencing of the human ε-globin gene.Blood cells, molecules & diseases · 2011Article
- Transient expression assay of Agamma-588 (A/G) mutations in the K562 cell line.Iranian biomedical journal · 2011Article
- Experimental validation of predicted mammalian erythroid cis-regulatory modules.Genome research · 2006Article
- DNA methylation supports intrinsic epigenetic memory in mammalian cells.PLoS genetics · 2006Article
- Article
- Evaluation of regulatory potential and conservation scores for detecting cis-regulatory modules in aligned mammalian genome sequences.Genome research · 2005Article
- The human beta-globin locus control region can silence as well as activate gene expression.Molecular and cellular biology · 2005Article
- Recruitment of transcription complexes to the beta-globin gene locus in vivo and in vitro.The Journal of biological chemistry · 2004Article
- Differential transcription factor occupancy but evolutionarily conserved chromatin features at the human and mouse M-CSF (CSF-1) receptor loci.Nucleic acids research · 2003Article
- Beta-globin locus control region HS2 and HS3 interact structurally and functionally.Nucleic acids research · 2003Article
- Chromatin insulation by a transcriptional activator.Proceedings of the National Academy of Sciences of the United States of America · 2003Article
- Requirements for utilization of CREB binding protein by hypersensitive site two of the beta-globin locus control region.Nucleic acids research · 2002Article
- The murine beta-globin locus control region regulates the rate of transcription but not the hyperacetylation of histones at the active genes.Proceedings of the National Academy of Sciences of the United States of America · 2001Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
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Abstract
The major distal regulatory sequence for the beta-globin gene locus, the locus control region (LCR), is composed of multiple hypersensitive sites (HSs). Different models for LCR function postulate that the HSs act either independently or synergistically. To test these possibilities, we have constructed a series of expression cassettes in which the gene encoding the enhanced green fluorescent protein (EGFP) is under the control of DNA fragments containing single and multiple HSs of the LCR. LCR DNA fragments containing only the minimal region needed for position-independent expression (HS cores) or containing cores plus flanking sequences (HS units) were compared to ascertain whether conserved sequences between the HS cores contributed to enhancement. Expression of these constructs was measured after targeted integration into three defined loci in murine erythroleukemia cells using recombinase-mediated cassette exchange. At all three marked loci, synergistic enhancement of expression was observed in cassettes containing a combination of HS2, HS3, and HS4 units. In contrast, HS2, HS3, and HS4 cores (without flanking sequences) give an activity equivalent to the sum of the activities of the individual HS cores. These data suggest a model in which an HS core plus flanking regions, bound by specific proteins, forms a structure needed for interaction with other HS units to confer strong enhancement by the LCR. The three targeted integration sites differ substantially in their permissivity for expression, but even the largest LCR construct tested could not overcome these position effects to confer equal expression at all three sites.
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