Cloning the cDNA for a new human zinc finger protein defines a group of closely related Kruppel-like transcription factors

Abstract

We have identified a novel zinc finger protein that has been named ubiquitous Kruppel-like factor (UKLF) based on structural considerations and the pattern of gene expression. UKLF was isolated by the polymerase chain reaction approach using degenerate oligonucleotides corresponding to the DNA- binding domain of erythroid Kruppel-like factor (EKLF) and cDNA prepared from human vascular endothelial cells. The carboxyl-terminal portion of UKLF contains three zinc fingers of the Cys2-His2 type and binds in vitro to the CACCC motif of the β-globin promoter and to the Sp1 recognition sequence. The amino-terminal portion of UKLF consists of a hydrophobic region rich in serines and a negatively charged segment with several glutamic acid residues. The first 47 amino acids of the acidic region are nearly identical to the amino-terminal portion of another Kruppel-like factor, the so-called core promoter-binding protein (CPBP) or Zf9. Like CPBP/Zf9, UKLF can function as a transcription activator in co-transfection assays. However, this activity is lost when the highly conserved amino-terminal segment is deleted. These findings indicate that UKLF and CPBP/Zf9 represent a distinct subgroup of closely related Kruppel-like activators of transcription. Mapping of the UKLF gene to chromosome 2 suggested that UKLF and CPBP/Zf9 translocated to different chromosomes following duplication from an ancestral gene.