ArticleProceedings of the National Academy of Sciences of the United States of America1997
Synergism between hypersensitive sites confers long-range gene activation by the beta-globin locus control region.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 42 citations in OpenAlex.
- Article
- Expression of green fluorescent protein under the regulation of human locus control region elements HS2 and HS3 in transgenic mice.International journal of hematology · 2008Article
- Article
- Bystander gene activation by a locus control region.The EMBO journal · 2004Article
- Beta-globin locus control region HS2 and HS3 interact structurally and functionally.Nucleic acids research · 2003Article
- Requirements for utilization of CREB binding protein by hypersensitive site two of the beta-globin locus control region.Nucleic acids research · 2002Article
- Sequences flanking hypersensitive sites of the beta-globin locus control region are required for synergistic enhancement.Molecular and cellular biology · 2001Article
- Developmentally dynamic histone acetylation pattern of a tissue-specific chromatin domain.Proceedings of the National Academy of Sciences of the United States of America · 2000Article
- Enhancement of beta-globin locus control region-mediated transactivation by mitogen-activated protein kinases through stochastic and graded mechanisms.Molecular and cellular biology · 1999Article
- Hypersensitive site 2 specifies a unique function within the human beta-globin locus control region to stimulate globin gene transcription.Molecular and cellular biology · 1999Article
- Deregulation of the proto-oncogene c-myc through t(8;22) translocation in Burkitt's lymphoma.Oncogene · 1999Article
- Mitogen-activated protein kinases enhance long-range activation by the beta-globin locus control region.Proceedings of the National Academy of Sciences of the United States of America · 1998Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
The human beta-globin locus control region (LCR) consists of four erythroid-specific DNaseI hypersensitive sites (HSs) at the 5' end of the beta-globin cluster. The LCR functions over a long distance on chromosome 11 to regulate transcription and replication of the beta-globin genes. To determine whether the HSs function independently or as an integrated unit, we analyzed the requirements for long-range transcriptional activation. If the HSs function independently, individual HSs would be expected to have long-range activity. In contrast, if long-range activity requires multiple HSs, individual HSs would have a limited functional distance. HS2, HS3, and a miniLCR containing multiple HSs, were separated from a gamma-globin promoter by fragments of phage lambda DNA. After stable transfection into K562 cells, HS2 had strong enhancer activity, but only when positioned close to the promoter. HS3 also had strong enhancer activity, although it was weaker than HS2 and more sensitive to the spacer DNA. The miniLCR had the strongest enhancer activity and functioned even at a distance of 7.3 kb. A model is proposed in which synergistic interactions between HSs confer long-range activation by creating a stable LCR nucleoprotein structure, which is competent for recruiting chromatin-modifying enzymes. These enzymes would mediate the well-characterized activity of the LCR to modulate chromatin structure.
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