Transcriptional Factors for Specific Globin Genesa

Correct temporal control of the beta-like globin cluster is generated in part by the binding of tissue-restricted transcriptional regulators to their cognate sites. Erythroid Krüppel-like Factor (EKLF) is one of these red cell-specific activators that is particularly important for switching on adult beta-globin gene expression. However, its simple presence is not sufficient to activate the beta-globin promoter, as primitive erythroid cells and a number of erythroid cell lines express EKLF yet do not express adult beta-globin. One explanation that may account for these observations is that post-translational modification of EKLF differs within these cell populations. To address this issue, we are investigating whether phosphorylation plays a role in modulating EKLF activity. In vitro and in vivo approaches have been used to demonstrate that EKLF is a phosphoprotein whose ability to bind DNA and transcriptionally activate an adjacent promoter is critically dependent on its phosphorylation status. Of particular interest is a casein kinase II site within the EKLF minimal transactivation domain.