HS5 of the human beta-globin locus control region: a developmental stage-specific border in erythroid cells.
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.
Wai
Albert W K
AW
Department of Cell Biology, Erasmus MC, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
Gillemans
Nynke
N
Raguz-Bolognesi
Selina
S
Pruzina
Sara
S
Zafarana
Gaetano
G
Meijer
Dies
D
Philipsen
Sjaak
S
Grosveld
Frank
F
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
D005914:Globins