Characterization of the Lmo4 gene encoding a LIM-only protein: Genomic organization and comparative chromosomal mapping

Abstract

LIM-only (LMO) proteins are transcription regulators that function by mediating protein-protein interaction and include the T cell oncogenes encoding LMO1 and LMO2. The oncogenic functions of LMO1 and LMO2 are thought to be mediated by interaction with LDB1 since they form a multimeric protein complex(es). A new member of the Lmo family, Lmo4, has also recently been identified via its interaction with Ldb1. Sequence analysis of the mouse Lmo4 gene shows that it spans about 18 kb and consists of at least six exons, including two alternatively spliced 5' exons. Unlike Lmo1, the two 5' exons of Lmo4 do not encode protein. Comparison of the Lmo4 gene structure with the other LMO family members shows the exon structure of Lmo4 differs in the position of exon junctions encoding the second LIM domain and in a novel exon-intron junction at the penultimate codon of the gene. Lmo4 is thus the least conserved known member of the LIM-only family in both nucleotide sequence and exon structure. Physical mapping of the Lmo4/LMO4 genes has shown mouse Lmo4 is located on Chromosome (Chr)3 and human LMO4 on Chr 1p22.3. This chromosome location is of interest as it occurs in a region that is deleted in a number of human cancers, indicating a possible role of LMO4 in tumorigenesis, like its relatives LMO1 and LMO2.