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Blood, Vol. 95 No. 11 (June 1), 2000:
pp. 3578-3584
FKLF-2: a novel Krüppel-like transcriptional factor that
activates globin and other erythroid lineage genes
Haruhiko Asano,
Xi Susan Li, and
George Stamatoyannopoulos
From the Division of Medical Genetics, University of Washington,
Seattle, WA.
FKLF-2, a novel Krüppel-type zinc finger protein, was cloned
from murine yolk sac. The deduced polypeptide sequence of 289 amino
acids has 3 contiguous zinc fingers at the near carboxyl-terminal end,
an amino-terminal domain characterized by its high content of alanine
and proline residues and a carboxyl-terminal domain rich in serine
residues. By Northern blot hybridization, the human homologue of FKLF-2
is expressed in the bone marrow and striated muscles and not in 12 other human tissues analyzed. FKLF-2 is constitutively expressed in
established cell lines with an erythroid phenotype, but it is
inconsistently expressed in cell lines with myeloid or lymphoid
phenotypes. The expression of FKLF-2 messenger RNA (mRNA) is
up-regulated after induction of mouse erythroleukemia cells. In
luciferase assays, FKLF-2 activates predominantly the  , and to a
lesser degree, the  and  globin gene promoters. The activation of
gene promoter does not depend on the presence of an HS2 enhancer.
FKLF-2 activates the promoter predominantly by interacting with the
CACCC box, and to a lesser degree through interaction with the TATA
box or its surrounding DNA sequences. FKLF-2 also activated all the
other erythroid specific promoters we tested (GATA-1, glycophorin B,
ferrochelatase, porphobilinogen deaminase, and 5-aminolevulinate
synthase). These results suggest that in addition to globin, FKLF-2 may
be involved in activation of transcription of a wide range of genes in
the cells of the erythroid lineage.
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