Nucleic Acids Research, Vol 25, Issue 6 1225-1232, Copyright © 1997 by Oxford University Press
PK Chan, FY Chan, SW Morris and Z Xie
NPM (nucleophosmin/B23) is a major nucleolar protein which is 20 times more
abundant in tumor or proliferating cells than in normal resting cells.
Recently, it was found that NPM gene is located at the breakpoints of the
t(2:5), t(3:5) and t(5:17) chromosome translocation. To understand the
human NPM gene's structure and regulation, four genomic clones were
isolated from the human chromosome 5 library and their DNA sequences
analyzed. The human NPM gene has 12 exons of sizes ranging from 58 to 358
bp. The chromosome breakpoint for t(2:5) and t(5:17) translocation is
within intron 4 and the breakpoint for t(3:5) translocation is within
intron 6. The initiation site is located 96 bp upstream from the ATG site.
A typical TATA box (at -25 nt) and a GC box (at -65 nt) were identified in
the promoter region. We identified two gel-shift bands (A and B) with DNA
fragment E (-741/-250 nt) by EMSA. A DNA footprint was observed at
(-371/-344 nt) with the nuclear extract. A double stranded DNA with the
footprint sequence (-371/-344 nt) competed the formation of gel-shift bands
A and B in EMSA suggesting that proteins A and B bind to the footprint
region. We confirmed that protein A is transcription factor YY1. These
results suggest that YY1 may play a role in NPM gene expression. This is
the first report on human NPM gene structure and sequence.
ARTICLES
Isolation and characterization of the human nucleophosmin/B23 (NPM) gene: identification of the YY1 binding site at the 5' enhancer region
Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030, USA. pchan@bcm.tmc.edu
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