Human alpha-globin genes demonstrate autonomous developmental regulation in transgenic mice.
Recent studies have demonstrated that transcriptional activation of the human adult beta-globin transgene in mice by coinsertion of the beta-globin cluster locus control region (beta-LCR) results in loss of its adult restricted pattern of expression. Normal developmental control is reestablished by coinsertion of the fetal gamma-globin transgene in cis to the adult beta-globin gene. To test the generality of this interdependence of two globin genes for their proper developmental control, we generated transgenic mice in which the human adult alpha-globin genes are transcriptionally activated by the beta-LCR either alone or in cis to their corresponding embryonic zeta-globin gene. In both cases, the human globin transgenes were expressed at the appropriate developmental period. In contrast to the beta-globin gene, developmental control of the human adult alpha-globin transgenes appears to be autonomous and maintained even when activated by an adjacent locus control region.
Albitar
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Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia 19104.
Katsumata
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Liebhaber
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SA
D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D003433:Crosses, Genetic; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005314:Embryonic and Fetal Development; D005260:Female; D005786:Gene Expression Regulation; D005914:Globins / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D005810:Multigene Family; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction / Q000379:methods; D012313:RNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics; D015183:Restriction Mapping; D012156:Reticulocytes / Q000502:physiology; D014158:Transcription, Genetic
D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D012313:RNA; D005914:Globins; D004247:DNA