ArticleMolecular and cellular biology2003
Human beta-globin locus control region HS5 contains CTCF- and developmental stage-dependent enhancer-blocking activity in erythroid cells.
Article in Molecular and cellular biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 56 citations in OpenAlex.
- Loop extrusion by cohesin plays a role in enhancer-activated gene expression early in differentiation.Nature communications · 2026Article
- Creating New β-Globin-Expressing Lentiviral Vectors by High-Resolution Mapping of Locus Control Region Enhancer Sequences.Molecular therapy. Methods & clinical development · 2020Article
- Improved Titer and Gene Transfer by Lentiviral Vectors Using Novel, Small β-Globin Locus Control Region Elements.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Transvection-like interchromosomal interaction is not observed at the transcriptional level when tested in the Rosa26 locus in mouse.PloS one · 2019Article
- Microfluidics-Based Chromosome Conformation Capture (3C) Technology for Examining Chromatin Organization with a Low Quantity of Cells.Analytical chemistry · 2018Article
- PADI4 acts as a coactivator of Tal1 by counteracting repressive histone arginine methylation.Nature communications · 2014Article
- 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
- The H19 imprinting control region mediates preimplantation imprinted methylation of nearby sequences in yeast artificial chromosome transgenic mice.Molecular and cellular biology · 2013Article
- Article
- Functional regulation of pre-B-cell leukemia homeobox interacting protein 1 (PBXIP1/HPIP) in erythroid differentiation.The Journal of biological chemistry · 2012Article
- Comprehensive identification and annotation of cell type-specific and ubiquitous CTCF-binding sites in the human genome.PloS one · 2012Article
- Kaposi's Sarcoma-Associated Herpesvirus Genome Replication, Partitioning, and Maintenance in Latency.Frontiers in microbiology · 2012Article
- In the loop: long range chromatin interactions and gene regulation.Briefings in functional genomics · 2011Review
- DNase I hypersensitivity and epsilon-globin transcriptional enhancement are separable in locus control region (LCR) HS1 mutant human beta-globin YAC transgenic mice.The Journal of biological chemistry · 2010Article
- Modular insulators: genome wide search for composite CTCF/thyroid hormone receptor binding sites.PloS one · 2010Article
- All of the human beta-type globin genes compete for LCR enhancer activity in embryonic erythroid cells of yeast artificial chromosome transgenic mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2009Article
- Multiple organ system defects and transcriptional dysregulation in the Nipbl(+/-) mouse, a model of Cornelia de Lange Syndrome.PLoS genetics · 2009Article
- Vertebrate Protein CTCF and its Multiple Roles in a Large-Scale Regulation of Genome Activity.Current genomics · 2009Article
- Gene specificity of suppression of transgene-mediated insertional transcriptional activation by the chicken HS4 insulator.PloS one · 2009Article
- An insulator with barrier-element activity promotes alpha-spectrin gene expression in erythroid cells.Blood · 2009Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
The human beta-globin locus contains five developmentally regulated beta-type globin genes. All five genes depend on the locus control region (LCR), located at the 5' end of the locus, for abundant globin gene transcription. The LCR is composed of five DNase I-hypersensitive sites (HSs), at least a subset of which appear to cooperate to form a holocomplex in activating genes within the locus. We previously tested the requirement for proper LCR polarity by inverting it in human beta-globin yeast artificial chromosome transgenic mice and observed reduced expression of all the beta-type globin genes regardless of developmental stage. This phenotype clearly demonstrated an orientation-dependent activity of the LCR, although the mechanistic basis for the observed activity was obscure. Here, we describe genetic evidence demonstrating that human HS5 includes enhancer-blocking (insulator) activity that is both CTCF and developmental stage dependent. Curiously, we also observed an attenuating activity in HS5 that was specific to the epsilon-globin gene at the primitive stage and was independent of the HS5 CTCF binding site. These observations demonstrate that the phenotype observed in the LCR-inverted locus was in part attributable to placing the HS5 insulator between the LCR HS enhancers (HS1 to HS4) and the promoter of the beta-globin gene.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.