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.

*Regulatory Sequences, Nucleic Acid, 0 (DNA-Binding Proteins), 0 (Transcription Factors), 125267-48-3 (erythroid-specific DNA-binding factor), 9004-22-2 (Globins), 9007-49-2 (dna), Animals, Base Sequence, DNA-Binding Proteins/metabolism, Dna, Globins/*genetics, Human, Mice, Mice, Transgenic, Molecular Sequence Data, Mutation, Support, Non-U.S. Gov't, Transcription Factors/metabolism, Zinc Fingers
hdl.handle.net/1765/2480
EMBO Journal
Erasmus MC: University Medical Center Rotterdam

Philipsen, J.N.J, Pruzina, S, & Grosveld, F.G. (1993). The minimal requirements for activity in transgenic mice of hypersensitive site 3 of the β globin locus control region. EMBO Journal, 12, 1077–1085. Retrieved from http://hdl.handle.net/1765/2480