The regulation of the differential expression of the human globin genes during development

Abstract

Although a great deal is known about the structure and molecular pathology of the human haemoglobin genes it is still not clear how their differential expression during normal development is regulated. As well as being of considerable interest to developmental geneticists, this problem has important practical implications. Variability in the expression of the foetal globin genes plays a major role in modifying the clinical course of some of the common genetic disorders of adult haemoglobin production. If it were possible to prevent the switching off of foetal haemoglobin production after the neonatal period, or to reactivate it even partially, we would have an extremely valuable approach to the management of these conditions, which are globally the commonest single gene disorders. Here the author shall summarize what has been learnt from the experimental systems that are being used to study the regulation of the developmental changes in globin gene expression. It will be possible to touch on only those areas that seem to be of particular promise for future work. Several recent reviews cover human haemoglobin genetics and the developmental biology of haemoglobin in more detail; original references to much of the experimental work described here will be found in these articles.