Human KRML (MAFB): cDNA Cloning, Genomic Structure, and Evaluation as a Candidate Tumor Suppressor Gene in Myeloid Leukemias

Abstract

Members of the MAF family of basic region/leucine zipper transcription factors can affect transcription in either a positive or a negative fashion, depending on their partner protein(s) and the context of the target promoter. The KRML (MAFB) transcriptional regulator plays a pivotal role in regulating lineage-specific hematopoiesis by repressing ETS1-mediated transcription of erythroid-specific genes in myeloid cells. In previous studies, we mapped the human KRML gene within a genomic contig on human chromosome 20, bands q11.2–q13.1. We have isolated the human cDNA containing the full-length predicted open reading frame (ORF). Multiple KRML transcripts of ∼1.8 and ∼3 kb, which differ in the length of the 3′ untranslated region, are ubiquitously expressed in hematopoietic tissues and encode a protein with 323 amino acids (MW 35,832). The protein has 84% identity and 92% similarity to the murine protein. The ORF of the human KRML gene contains no introns, and the gene spans ∼3 kb. KRML maps within the smallest commonly deleted segment in malignant myeloid disorders characterized by a deletion of 20q; however, we detected no mutations of KRML in leukemia cells with loss of 20q. Thus, KRML is unlikely to be involved in the pathogenesis of malignant myeloid disorders characterized by abnormalities of chromosome 20.