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. 1993 Mar;12(3):1077–1085. doi: 10.1002/j.1460-2075.1993.tb05749.x

The minimal requirements for activity in transgenic mice of hypersensitive site 3 of the beta globin locus control region.

S Philipsen 1, S Pruzina 1, F Grosveld 1
PMCID: PMC413309  PMID: 8458325

Abstract

Proper expression of the human beta-like globin genes is completely dependent on the presence of the locus control region or LCR, a region containing four DNase hypersensitive sites (HS1-4) situated 5' to the structural genes. Linkage of the LCR to a transgene results in copy number-dependent transcription, independent of the site of integration in the host genome. We have analysed a small region of the LCR (HS3) in transgenic animals to determine the minimal interactions that are required for this property. The results show that a specific combination of a G-rich sequence flanked on each side by one binding site for the transcription factor GATA1 is essential to obtain position-independent expression of a linked beta globin gene in erythroid cells. The overall transcriptional activity of HS3 is achieved through synergy with other combinations of similar binding sites.

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