ArticleThe EMBO journal1995
Targeting gene expression to haemopoietic stem cells: a chromatin-dependent upstream element mediates cell type-specific expression of the stem cell antigen CD34.
Article in The EMBO journal, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 47 citations in OpenAlex.
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- Locus control regions.Blood · 2002Review
- Establishing the transcriptional programme for blood: the SCL stem cell enhancer is regulated by a multiprotein complex containing Ets and GATA factors.The EMBO journal · 2002Article
- Dividing the empire: boundary chromatin elements delimit the territory of enhancers.The EMBO journal · 1999Review
- p45 NF-E2 regulates expression of thromboxane synthase in megakaryocytes.The EMBO journal · 1997Article
- Chicken vigilin gene: a distinctive pattern of hypersensitive sites is characteristic for its transcriptional activity.The Biochemical journal · 1997Article
- An upstream, DNase I hypersensitive region of the hematopoietic-expressed transcription factor GATA-1 gene confers developmental specificity in transgenic mice.Proceedings of the National Academy of Sciences of the United States of America · 1997Article
- A lineage-selective knockout establishes the critical role of transcription factor GATA-1 in megakaryocyte growth and platelet development.The EMBO journal · 1997Article
- The beta-globin locus control region enhances transcription of but does not confer position-independent expression onto the lacZ gene in transgenic mice.The EMBO journal · 1996Article
- The human growth hormone gene is regulated by a multicomponent locus control region.Molecular and cellular biology · 1995Article
- Sp1 functions in a chromatin-dependent manner to augment human alpha-globin promoter activity.Proceedings of the National Academy of Sciences of the United States of America · 1995Article
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ability to target heterologous gene expression to haemopoietic stem cells will allow biological manipulation of this compartment and facilitate gene therapy of blood disorders. To identify regulatory elements with this potential, we have analysed the transcriptional regulation of the murine stem cell antigen CD34. Within haemopoiesis CD34 is expressed in stem and early progenitor cells, but it is also expressed in certain non-haemopoietic cell types, including fibroblasts. Comparison of CD34 chromatin in haemopoietic progenitor cells (416B and M1) and fibroblasts (Swiss 3T6) revealed several DNase I hypersensitive regions, one of which, a cluster of sites centred 3 kb upstream of exon 1, was specific to haemopoietic progenitors. This element stimulated expression by approximately two orders of magnitude in CD34+ haemopoietic progenitors, but not in CD34+ fibroblasts or in CD34- haemopoietic cells (18.8). Enhancer function was dependent upon chromosomal integration, although position-independent expression was not obtained. However, largely position-independent expression was conferred by addition of a downstream element which was hypersensitive in all the cell types analysed. We conclude that the murine CD34 gene is regulated by a chromatin-dependent, upstream enhancer element which acts in conjunction with a downstream domain-controlling element to confer high level gene expression in haemopoietic progenitor cells.
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