Mount Sinai School of Medicine, Brookdale Center for Molecular Biology, One Gustave L. Levy Place, New York, New York 10029, USA
Correct temporal control of the ß-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 ß-globin
gene expression. However, its simple presence is not sufficient
to activate the ß-globin promoter, as primitive erythroid
cells and a number of erythroid cell lines express EKLF yet
do not express adult ß-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.
