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

The gamma genes provide the major contribution to beta-like globin chain production in the fetal liver of humans. However, the expression of gamma 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 gamma genes retain their characteristic stage-specific expression patterns in transgenic mice (galago gamma is expressed exclusively in the embryo, whereas human gamma is expressed in the fetus). In that experiment, human and galago gamma 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 gamma genes were linked to HS2. Once again, the galago gamma gene was embryonic and the human gamma 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 gamma genes proper.