Abstract
Transcription of the human β-like globin genes in erythroid cells is regulated by the far-upstream locus control region (LCR). In an attempt to define the 5′ border of the LCR, we have cloned and sequenced 5 kb of new upstream DNA. We found an LTR retrotransposon belonging to the ERV-9 family of human endogenous retroviruses in the apparent 5′ boundary area of the LCR. This ERV-9 LTR contains an unusual U3 enhancer region composed of 14 tandem repeats with recurrent GATA, CACCC, and CCAAT motifs. This LTR is conserved in human and gorilla, indicating its evolutionary stability in the genomes of the higher primates. In both recombinant constructs and the endogenous human genome, the LTR enhancer and promoter activate the transcription ofcis-linked DNA preferentially in erythroid cells. Our findings suggest the possibility that this LTR retrotransposon may serve a relevant host function in regulating the transcription of the β-globin LCR.
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