Genomic sequence, structural organization, molecular evolution, and aberrant rearrangement of promyelocytic leukemia zinc finger gene

The promyelocytic leukemia zinc finger gene (PLZF) is involved in chromosom al translocation t(11;17) associated with acute promyelocytic leukemia. In this work a 201-kilobase genomic DNA region containing the entire PLZF gene was sequenced. Repeated elements account for 19.83%, and no obvious coding information other than PLZF is present over this region. PLZF contains six exons and five introns, and the exon organization corresponds well with pr otein domains. There are at least four alternative splicings (AS-I, -II, -I II, and -IV) within exon 1. AS-I could be detected in most tissues tested w hereas AS-II, -III, and -IV were present in the stomach, testis, and heart, respectively. Although splicing donor and acceptor signals at exon-intron boundaries for AS-I and exons 1-6 were classical (gt-ag), AS-II, -III, and -IV had atypical splicing sites. These alternative splicings, nevertheless, maintained the ORF and may encode isoforms with absence of important funct ional domains. In mRNA species without AS-I, there is a relatively long 5' UTR of 6.0 kilobases. A TATA box and several transcription factor binding s ites were found in the putative promoter region upstream of the transcripti on start site. PLZF is a well conserved gene from Caenorhabditis elegans to human. PLZF paralogous sequences are found in human genome. The presence o f two MLL/PLZF-like alignments on human chromosome 11q23 and 19 suggests a syntenic replication during evolution. The chromosomal breakpoints and join ing sites in the index acute promyelocytic leukemia case with t(11;17) also were characterized, which suggests the involvement of DNA damage-repair me chanism.