title: Genomic sequence, structural organization, molecular evolution, and aberrant rearrangement of promyelocytic leukemia zinc finger gene.
abstract: The promyelocytic leukemia zinc finger gene (PLZF) is involved in chromosomal 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 protein domains. There are at least four alternative splicings (AS-I, -II, -III, and -IV) within exon 1. AS-I could be detected in most tissues tested whereas 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 functional 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 sites were found in the putative promoter region upstream of the transcription start site. PLZF is a well conserved gene from Caenorhabditis elegans to human. PLZF paralogous sequences are found in human genome. The presence of two MLL/PLZF-like alignments on human chromosome 11q23 and 19 suggests a syntenic replication during evolution. The chromosomal breakpoints and joining sites in the index acute promyelocytic leukemia case with t(11;17) also were characterized, which suggests the involvement of DNA damage-repair mechanism.
authors.affiliation: Key Laboratory of Human Genome Research, Ministry of Public Health, Ruijin Hospital, Shanghai 200025, USA.
authors.forename: T
authors.initials: T
authors.lastname: Zhang
authors.forename: H
authors.initials: H
authors.lastname: Xiong
authors.forename: L X
authors.initials: LX
authors.lastname: Kan
authors.forename: C K
authors.initials: CK
authors.lastname: Zhang
authors.forename: X F
authors.initials: XF
authors.lastname: Jiao
authors.forename: G
authors.initials: G
authors.lastname: Fu
authors.forename: Q H
authors.initials: QH
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Lu
authors.forename: J H
authors.initials: JH
authors.lastname: Tong
authors.forename: B W
authors.initials: BW
authors.lastname: Gu
authors.forename: M
authors.initials: M
authors.lastname: Yu
authors.forename: J X
authors.initials: JX
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Licht
authors.forename: S
authors.initials: S
authors.lastname: Waxman
authors.forename: A
authors.initials: A
authors.lastname: Zelent
authors.forename: E
authors.initials: E
authors.lastname: Chen
authors.forename: S J
authors.initials: SJ
authors.lastname: Chen
mesh_terms: D017398:Alternative Splicing; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons; D015321:Gene Rearrangement; D005809:Genes, Regulator; D006801:Humans; D007438:Introns; D051741:Kruppel-Like Transcription Factors; D008969:Molecular Sequence Data; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D018168:Receptors, Retinoic Acid / Q000235:genetics; D011995:Recombination, Genetic; D000072482:Retinoic Acid Receptor alpha; D016385:TATA Box; D014157:Transcription Factors / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors; C092037:ZBTB16 protein, human