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

T Zhang; H Xiong; L.-X Kan; C.-K Zhang; X.-F Jiao; G Fu; Q.-H Zhang; L Lu; J.-H Tong; B.-W Gu; M Yu; J.-X Liu; J Licht; S Waxman; A Zelent; E Chen; S.-J Chen

doi:10.1073/pnas.96.20.11422

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

Journal article

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

T Zhang, H Xiong, L.-X Kan, C.-K Zhang, X.-F Jiao, G Fu, Q.-H Zhang, L Lu, J.-H Tong, B.-W Gu, …

Proceedings of the National Academy of Sciences - PNAS, Vol.96(20), pp.11422-11427

1999-09-28

DOI: https://doi.org/10.1073/pnas.96.20.11422

PMCID: PMC18049

PMID: 10500192

Abstract

Biological Sciences

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.

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Title: Genomic sequence, structural organization, molecular evolution, and aberrant rearrangement of promyelocytic leukemia zinc finger gene
Creators: T Zhang - Key Laboratory of Human Genome Research, Ministry of Public Health and Shanghai Municipality, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025
H Xiong - Key Laboratory of Human Genome Research, Ministry of Public Health and Shanghai Municipality, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025
L.-X Kan - Key Laboratory of Human Genome Research, Ministry of Public Health and Shanghai Municipality, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025
C.-K Zhang - Key Laboratory of Human Genome Research, Ministry of Public Health and Shanghai Municipality, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025
X.-F Jiao - Key Laboratory of Human Genome Research, Ministry of Public Health and Shanghai Municipality, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025
G Fu - Key Laboratory of Human Genome Research, Ministry of Public Health and Shanghai Municipality, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025
Q.-H Zhang - Key Laboratory of Human Genome Research, Ministry of Public Health and Shanghai Municipality, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025
L Lu - Key Laboratory of Human Genome Research, Ministry of Public Health and Shanghai Municipality, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025
J.-H Tong - Key Laboratory of Human Genome Research, Ministry of Public Health and Shanghai Municipality, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025
B.-W Gu - Key Laboratory of Human Genome Research, Ministry of Public Health and Shanghai Municipality, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025
M Yu - Key Laboratory of Human Genome Research, Ministry of Public Health and Shanghai Municipality, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025
J.-X Liu - Key Laboratory of Human Genome Research, Ministry of Public Health and Shanghai Municipality, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025
J Licht - Key Laboratory of Human Genome Research, Ministry of Public Health and Shanghai Municipality, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025
S Waxman - Key Laboratory of Human Genome Research, Ministry of Public Health and Shanghai Municipality, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025
A Zelent - Key Laboratory of Human Genome Research, Ministry of Public Health and Shanghai Municipality, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025
E Chen - Key Laboratory of Human Genome Research, Ministry of Public Health and Shanghai Municipality, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025
S.-J Chen - Key Laboratory of Human Genome Research, Ministry of Public Health and Shanghai Municipality, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.96(20), pp.11422-11427
Publisher: The National Academy of Sciences
Language: English
Resource Type: Journal article
PMID: 10500192
PMCID: PMC18049
Record Identifier: 991031614831002976