posted on 2008-01-22, 00:00authored byLouis J. Lurie, Meghan E. Boyer, Jeffrey A. Grass, Emery H. Bresnick
Whereas the transcription factors GATA-1 and GATA-2 function both uniquely and redundantly
to control blood cell development, the process termed hematopoiesis, mechanisms underlying their unique
versus common functions are poorly understood. We used two independent assays to demonstrate that
GATA-1 is considerably more stable than GATA-2 in multiple cellular contexts, even though both factors
are subject to degradation via the ubiquitin−proteasome system. Studies with GATA factor mutants and
novel chimeric GATA factors provided evidence that both GATA-1 and GATA-2 have highly unstable
zinc finger core modules. The GATA-1 and GATA-2 N-termini both confer stabilization to their respective
zinc finger core modules. In contrast, the GATA-1 and GATA-2 C-termini confer stabilization and
destabilization, respectively. As GATA-2 stabilization via proteasome inhibition impairs the capacity of
GATA-1 to displace GATA-2 from endogenous chromatin sites, we propose that differential GATA factor
stability is an important determinant of chromatin target site occupancy and therefore the establishment
of genetic networks that control hematopoiesis.