Regulation of fetal versus embryonic gamma globin genes: appropriate developmental stage expression patterns in the presence of HS2 of the locus control region.

The γ genes provide the major contribution to beta-like globin chain production in the fetal liver of humans. However, the expression of γ genes in the fetus is a recent evolutionary trend seen only in the primate lineage. In a previous study, it was shown that galago and human γ genes retain their characteristic stage-specific expression patterns in transgenic mice (galago γ is expressed exclusively in the embryo, whereas human γ is expressed in the fetus). In that experiment, human and galago γ genes were linked to hypersensitive site 3 (HS3) of the locus control region. To rule out the possibility that HS3 is required for these differential expression profiles, additional transgenic lines were tested in which human or galago γ genes were linked to HS2. Once again, the galago γ gene was embryonic and the human γ gene was fetal, indicating that the stage specificity of these genes is driven by elements located within the 4-kb fragments that contain the human and galago γ genes proper.