NF-E2 belongs to the basic-leucine zipper family of dimeric transcript
ion factors. It consists of a widely expressed 18 kDa subunit, related
to chicken Maf proteins, and a tissue-restricted 45 kDa subunit, whic
h contains a cnc domain. It is found almost exclusively in hematopoiet
ic progenitors, and cells of the erythroid/mega/mast cell trilineage.
NF-E2 is involved in regulation of globin gene transcription, acting t
hrough locus control regions (LCRs) upstream of the alpha and beta glo
bin gene clusters. In addition, it is essential for normal platelet pr
oduction. Targeted disruption of the gene encoding the 45 kDa subunit
leads to severe thrombocytopenia but little if any defect in erythropo
iesis, indicating that other molecules can substitute for p45 in red c
ell maturation in developing mice. However, retroviral integration wit
hin the p45 gene has been shown to disrupt erythroid differentiation i
n erythroleukemia cells; this suggests that p45 could, conceivably, be
a target for pharmacologic interventions in patients with excess red
cell production due to polycythemia vera. (C) 1998 Elsevier Science Lt
d. All rights reserved.