Developmental regulation of human beta-globin gene transcription: a switch of loyalties?

Synthesis of different hemoglobin polypeptides during the early stages of human development is principally regulated by transcriptional control mechanisms that determine which of the five beta-type globin genes is expressed. The means by which this is achieved have been scrutinized for several decades, and insights have been gained from introducing segments of the human beta-globin locus into transgenic mice, and from analysis of naturally occurring mutations at the locus. I describe here a model which attempts to resolve several of the current puzzles and provides simple, testable predictions for how differential beta-globin gene transcription might be achieved during human development.