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J Biol Chem, Vol. 273, Issue 50, 33848-33855, December 11, 1998
Cloning and Characterization of the Human
4-Integrin Gene Promoter and Enhancers
Asako Suzuki
Takaoka §,
Tesshi
Yamada ,
Masahiro
Gotoh ,
Yae
Kanai ,
Kohzoh
Imai§, and
Setsuo
Hirohashi
From the Pathology Division, National Cancer Center
Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 and
the § First Department of Internal Medicine, Sapporo Medical
University School of Medicine, Minami-1,
Nishi-16, Chuo-ku, Sapporo 060-8543, Japan
The cell-surface adhesion molecule
6 4-integrin is a receptor for
laminins and a component of hemidesmosomes. 4-Integrin expression is restricted to proliferating basal keratinocytes in the
epidermis and is suppressed when differentiation commences. Altered
4-integrin expression levels correlate significantly with the aggressive behavior of cancers. In order to clarify the mechanisms that regulate transcription of the 4-integrin
gene, we cloned its 5'-flanking region. This 5'-flanking region was found to have a high G + C content and not to contain either TATA or
CAAT boxes. Nested delimitation and reporter analyses mapped a basal
promoter to nucleotides 106 to +105, surrounding the most proximal
transcription initiation site. Gel retardation and mutational analyses
revealed that cooperation between AP1 and Ets, interacting with other
factors, mediated the promoter activity. In addition to the promoter
element, enhancer activity was found in the first intron (+1905/+3933)
and in a sequence upstream of the promoter region ( 414/ 107). These
findings should facilitate our understanding of the regulation of
4-integrin gene expression in processes such as cell
growth and differentiation, apoptosis, and cancer development and metastasis.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 1998 by the American Society for Biochemistry and Molecular Biology.
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