ArticleProceedings of the National Academy of Sciences of the United States of America2001
The murine beta-globin locus control region regulates the rate of transcription but not the hyperacetylation of histones at the active genes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29 citing papers in PubMed, 85 citations in OpenAlex.
- Super-enhancers include classical enhancers and facilitators to fully activate gene expression.Cell · 2023Article
- A structural hierarchy mediated by multiple nuclear factors establishes IgH locus conformation.Genes & development · 2015Article
- Developmental variation of the SUUR protein binding correlates with gene regulation and specific chromatin types in D. melanogaster.Chromosoma · 2014Article
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- Distinct chromatin configurations regulate the initiation and the maintenance of hGH gene expression.Molecular and cellular biology · 2013Article
- 3D shortcuts to gene regulation.Current opinion in cell biology · 2010Review
- Structure and epigenetics of nucleoli in comparison with non-nucleolar compartments.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2010Review
- Enhancers: the abundance and function of regulatory sequences beyond promoters.Developmental biology · 2010Review
- Article
- A 220-nucleotide deletion of the intronic enhancer reveals an epigenetic hierarchy in immunoglobulin heavy chain locus activation.The Journal of experimental medicine · 2009Article
- Article
- The locus control region activates serpin gene expression through recruitment of liver-specific transcription factors and RNA polymerase II.Molecular and cellular biology · 2007Article
- Intergenic transcription, cell-cycle and the developmentally regulated epigenetic profile of the human beta-globin locus.PloS one · 2007Article
- Article
- The locus control region is required for association of the murine beta-globin locus with engaged transcription factories during erythroid maturation.Genes & development · 2006Article
- Activation of the chicken Ig-beta locus by the collaboration of scattered regulatory regions through changes in chromatin structure.Nucleic acids research · 2006Article
- Synergistic and additive properties of the beta-globin locus control region (LCR) revealed by 5'HS3 deletion mutations: implication for LCR chromatin architecture.Molecular and cellular biology · 2005Article
- Developmental stage differences in chromatin subdomains of the beta-globin locus.Proceedings of the National Academy of Sciences of the United States of America · 2004Article
- A human globin enhancer causes both discrete and widespread alterations in chromatin structure.Molecular and cellular biology · 2003Article
- A complex chromatin landscape revealed by patterns of nuclease sensitivity and histone modification within the mouse beta-globin locus.Molecular and cellular biology · 2003Article
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Authors and funding
3 authors at 2 institutions in 1 country.
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Abstract
Locus control regions (LCRs) are defined by their ability to confer high-level tissue-specific expression to linked genes in transgenic assays. Previously, we reported that, at its native site, the murine beta-globin LCR is required for high-level beta-globin gene expression, but is not required to initiate an open chromatin conformation of the locus. To further investigate the mechanism of LCR-mediated transcriptional enhancement, we have analyzed allele-specific beta-globin expression and the pattern of histone acetylation in the presence and absence of the LCR. In single cells from mice heterozygous for a deletion of the LCR, beta-globin expression from the LCR-deleted allele is consistently low ( approximately 1-4% of wild type). Thus, the endogenous LCR enhances globin gene expression by increasing the rate of transcription from each linked allele rather than by increasing the probability of establishing transcription per se. Furthermore, in erythroid cells from mice homozygous for the highly expressing wild-type beta-globin locus, hyperacetylation of histones H3 and H4 is localized to the LCR and active genes. In mice homozygous for the LCR deletion reduced histone hyperacetylation is observed in LCR proximal sequences; however, deletion of the LCR has no effect on the localized hyperacetylation of the genes. Together, our results suggest that, in its native genomic context, the LCR follows the rate model of enhancer function, and that the developmentally specific hyperacetylation of the globin genes is independent of both the rate of transcription and the presence of the LCR.
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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.