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Transcriptional activation by hypersensitive site three of the human β-globin locus control region in murine erythroleukemia cells

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Abstract

In this paper we describe a complete deletional analysis of hypersensitive site three (HS3) of the human β-globin Locus Control Region (LCR). The previously defined core fragment consists of 6 footprinted regions, with multiple binding sites for the erythroid-specific factor GATA-1 and G-rich motifs that can interact with ubiquitous factors such as Sp1 and TEF-2. We show in this paper that the 5′ half of this fragment is the most important for activity in murine erythroleukemia (MEL) cells. A fragment containing footprints 1–4 can stimulate transcription of a linked human β-globin gene to levels of about 40% of that obtained with footprints 1–6. Constructs containing either footprints 1–3 or 3–6 cannot be distinguished from the β-globin gene alone. We further show that binding sites for the erythroid-specific factor NF-E2 can co-operatively interact with parts of the HS3 core fragment, and that HS3 requires elements upstream from −103 in the human β-globin promoter for full activity. The importance of these results is discussed in the context of the regulation of the genes in the human β-globin cluster.

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    Present address: MGC, Department of Cell Biology and Genetics, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.

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