The proximal element of the β globin locus control region is not functionally required in vivo

Abstract

In addition to local sequence elements the regulation of the high-level, development- and tissue-specific expression of the human β globin gene cluster appears to require distant regulatory sequences which have been termed locus control region. In the chromatin of erythroid cells the locus control region is characterized by four DNaseI hypersensitive sites that are located 6-18 kb 5′ of the ∈ globin gene. The definition of the sequences minimally required for locus control region activity is likely to further the understanding of its physiology and will be of interest for the development of somatic gene therapy strategies of the hemoglobinopathies. We present here the analysis of a family with a 3,030-bp deletion of sequences upstream of the ∈ globin gene including the most 3′ locus control region element and cosegregating β°thalassemia. The deletion is linked in cis to a structurally and functionally normal β globin gene. The proximal element of the locus control region does not therefore appear to be necessary for β globin gene activity in vivo.