Kp. Anderson et al., ISOLATION OF A GENE ENCODING A FUNCTIONAL ZINC-FINGER PROTEIN HOMOLOGOUS TO ERYTHROID KRUPPEL-LIKE FACTOR - IDENTIFICATION OF A NEW MULTIGENE FAMILY, Molecular and cellular biology, 15(11), 1995, pp. 5957-5965
We have identified and characterized the gene for a novel zinc finger
transcription factor which we have termed lung Kruppel-like factor (LK
LF). LKLF was isolated through the use of the zinc finger domain of er
ythroid Kruppel-like factor (ELKF) as a hybridization probe and is clo
sely related to this erythroid cell-specific gene. LKLF is expressed i
n a limited number of tissues, with the predominant expression seen in
the lungs and spleen. The gene is developmentally controlled, with ex
pression noted in the 7-day embryo followed by a down-regulation at 11
days and subsequent reactivation. A high degree of similarity is note
d in the zinc finger regions of LKLF and EKLF. Beyond this domain, the
sequences diverge significantly, although the putative transactivatio
n domains for both LKLF and EKLF are proline-rich regions. In the DNA-
binding domain, the three zinc finger motifs are so closely conserved
that the predicted DNA contact sites are identical, suggesting that bo
th proteins may bind to the same core sequence. This was further sugge
sted by transactivation assays in which mouse fibroblasts were transie
ntly transfected with a human beta-globin reporter gene in the absence
and presence of an LKLF cDNA construct. Expression of the LKLF gene a
ctivates this human beta-globin promoter containing the CACCC sequence
previously shown to be a binding site for EKLF. Mutation of this pote
ntial binding site results in a significant reduction in the reporter
gene expression. LKLF and EKLF can thus be grouped as members of a uni
que family of transcription factors which have discrete patterns of ex
pression in different tissues and which appear to recognize the same D
NA-binding site.