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(Received for publication, December 29, 1995, and in revised form, March 14, 1996)
From the Sidney Kimmel Cancer Center,
San Diego, California 92121
An Alu element preceding the myeloperoxidase gene
(MPO) contains four hexamer motifs related to the consensus
recognition sequence for nuclear hormone receptors (AGGTCA), arranged
as direct repeats with spacing of 2, 4, and 2 nucleotides (DR-2-4-2).
Gel shift experiments and transient transfection assays demonstrate
that these sequences include binding sites for retinoic acid and
thyroid hormone receptors and function in vivo to activate
transcription of a chloramphenicol acetyltransferase reporter gene. The
first DR-2 elements of the series do not bind known receptors but do
bind the SP1 transcription factor. Two alleles of the MPO
gene exist that differ at one position within this element, resulting
in one allele with and one without a strong SP1 binding site. The
element with the SP1 site activates transcription by 25-fold in
transient transfection assays, while the alternative allele confers
severalfold less transcriptional activity. Most cases of acute
myelocytic leukemia are homozygous for the allele with the SP1 binding
site, suggesting this element plays an important role in regulating the
MPO gene in myeloid leukemias. This MPO-Alu is
a representative of an Alu subclass numbering ~400,000 copies,
suggesting many genes may be regulated by such elements.
Volume 271, Number 24,
Issue of June 14, 1996
pp. 14412-14420
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
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