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J Biol Chem, Vol. 274, Issue 40, 28794-28802, October 1, 1999
From the Division of Pediatric Hematology/Oncology, Department of
Pediatrics and Communicable Diseases, University of Michigan School of
Medicine, Ann Arbor, Michigan 48109
MXI1, a member of the MAD
family of Myc antagonists, encodes a transcription factor whose
expression must be tightly regulated to maintain normal cell growth and
differentiation. To more closely investigate the transcriptional
regulation of the human MXI1 gene, we have cloned and
characterized the MXI1 promoter. After clarification of the
5'- and 3'-untranslated regions of the cDNA (indicating that the
true length of the MXI1 transcript is 2643 base pairs), we
identified two transcription initiation sites. We subsequently isolated
the MXI1 promoter, which is GC-rich and lacks a TATA box.
Although it contains at least six potential initiator sequences, functional studies indicate the proximal two initiator sequences in
combination with nearby Sp1 and MED-1 sites together account for
virtually all promoter activity. We also demonstrate that MXI1 promoter activity is repressed by high levels of AP2.
These studies provide further insight into the complex regulatory
mechanisms governing MXI1 gene expression and its role in
cellular differentiation and tumor suppression.
Expression of MXI1, a Myc Antagonist, Is
Regulated by Sp1 and AP2
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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