The Murine L-plastin Gene Promoter: Identification and Comparison with the Human L-plastin Gene Promoter

Abstract

Plastins (or fimbrins) are a family of actin-binding proteins that are conserved from yeast to humans. In mammals, three tissue-specific plastin isoforms have been identified. The L isoform (L-plastin) is normally expressed only in leukocytes but is also found in >90% of neoplastic nonleukocyte human cells. Because L-plastin expression in tissue-specifically regulated in both humans and rodents, it is likely that similar mechanisms regulate L-plastin gene expression in human and rodent cells and that they could be identified by comparing the function and nucleotide sequences of the human and murine L-plastin gene promoters. Previously, we reported the isolation and characterization of the human L-plastin gene promoter. In this study, we isolated a murine L-plastin 5' end cDNA and used it as a probe to isolate several murine genomic clones. A representative clone contained 7 kb of the flanking region, 0.1 kb of the first exon, and 9.9 kb of the first intron. A continuous 1,354-bp sequence was identified around the first exon. Five transcription initiation sites were found 40 to 73 bp downstream from a perfect TATA box. Alignment of the sequence with its human counterpart revealed approximately 60% homology in a 1-kb region spanning the first exon and the flanking region. The TATA box, one ER binding site, and two ETS binding sites were completely conserved. An Sp1 binding sequence in the human promoter was partially conserved in the murine promoter but could still bind to Sp1. A second ER binding sequence, lying 5' adjacent to the TATA box in the human promoter, was conserved only at the 3' half-site in the murine promoter; the 5' half-site was changed into a potential AP1 binding site. This AP1/ER hybrid sequence was incapable of binding to ER. However, both human and murine promoters were found to function equally well in either human or murine leukocytes.

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