Blood, 15 October 2001, Vol. 98, No. 8, pp. 2291-2292
C/EBP
and the G-CSF receptor gene - partners in
granulopoiesis?
The C/EBPs are a protein family with highly homologous
leucine zipper domains designed to allow dimerization within the
family. The finding that C/EBPs bind DNA as obligate homodimers or
heterodimers made combinatorial diversity relevant to the regulation of
developmental programs by transcription factors, just as antibody
diversity generated via combinations of light and heavy chains is a key component of the immune response. The additional discovery that C/EBPs
bind a common DNA motif raises a question: Is there selectivity in gene
regulation by C/EBPs? The observation that C/EBP
(
/) neonates
lack both neutro-phils and G-CSF-responsive progenitors combined
with evidence implicating C/EBPs as activators of the G-CSF receptor
gene answered this question in the affirmative. However, in this issue
(page 2382) Collins and his colleagues demonstrate high-level G-CSF
receptor expression in hematopoietic cells immortalized from C/EBP
(/) mice. How might these new data be reconciled with the lack of
CFU-G in the knockout mice? One possibility, perhaps the simplest, is
that while C/EBP is the most prominent C/EBP isoform in normal
granu-locytic progenitors, their immortalization via
expression of a dominant-negative retinoic acid receptor increases
expression of other family members, such as C/EBP
or C/EBP
.
Alternatively, the immortalized stem cells may have altered expression
of other factors capable of activating the G-CSF receptor promoter.
Regardless of the true explanation, C/EBP and the G-CSF receptor
gene can no longer be considered obligate partners.
Alan D. Friedman
Johns Hopkins University
