title: HS5 of the human beta-globin locus control region: a developmental stage-specific border in erythroid cells.
abstract: Elements with insulator/border activity have been characterized most extensively in Drosophila melanogaster. In vertebrates, the first example of such an element was provided by a hypersensitive site of the chicken beta-globin locus, cHS4. It has been proposed that the homologous site in humans, HS5, functions as a border of the human beta-globin locus. Here, we have characterized HS5 of the human beta-globin locus control region. We have examined its tissue-specificity and assessed its insulating properties in transgenic mice using a lacZ reporter assay. Most importantly, we have tested its enhancer blocking activity in the context of the full beta-globin locus. Our results show that HS5 is erythroid-specific rather than ubiquitous in human tissues. Furthermore, HS5 does not fulfil the criteria of a general in vivo insulator in the transgene protection assay. Finally, a HS5 conditional deletion from the complete locus demonstrates that HS5 has no discernable activity in adult erythroid cells. Surprisingly, HS5 functions as an enhancer blocker in embryonic erythroid cells. We conclude that HS5 is a developmental stage-specific border in erythroid cells.
authors.affiliation: Department of Cell Biology, Erasmus MC, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
authors.forename: Albert W K
authors.initials: AW
authors.lastname: Wai
authors.forename: Nynke
authors.initials: N
authors.lastname: Gillemans
authors.forename: Selina
authors.initials: S
authors.lastname: Raguz-Bolognesi
authors.forename: Sara
authors.initials: S
authors.lastname: Pruzina
authors.forename: Gaetano
authors.initials: G
authors.lastname: Zafarana
authors.forename: Dies
authors.initials: D
authors.lastname: Meijer
authors.forename: Sjaak
authors.initials: S
authors.lastname: Philipsen
authors.forename: Frank
authors.initials: F
authors.lastname: Grosveld
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D004331:Drosophila melanogaster / Q000235:genetics; D004920:Erythropoiesis / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D005914:Globins / Q000235:genetics*; D006801:Humans; D007763:Lac Operon; D019901:Locus Control Region; D051379:Mice; D008822:Mice, Transgenic; D015533:Transcriptional Activation
chemical_list: D005914:Globins