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J. Biol. Chem., Vol. 265, Issue 26, 15537-15543, Sep, 1990
RJ Allore, WC Friend, D O'Hanlon, KM Neilson, R Baumal, RJ Dunn and A Marks
S100 protein is a low molecular weight, EF-hand, Ca2(+)-binding protein
widely distributed and conserved in the central nervous system of
vertebrates. The gene coding for the beta subunit of human S100 protein
(S100 beta) has been recently mapped to chromosome 21. In order to study
the expression of this gene in normal and abnormal brain development, we
have isolated and characterized overlapping genomic clones spanning the
region coding for human S100 beta and its flanking sequences. The
intron-exon organization of the human S100 beta gene is similar to that of
the genes coding for several other members of the S100 protein subfamily of
EF-hand proteins. The human S100 beta gene is composed of 3 exons, the
first of which specifies the 5'-untranslated region, while the second and
third each encode a single EF-hand, Ca2(+)- binding domain. The promoter
region contains several potential regulatory transcription elements
including the cAMP-responsive elements CRE and AP-2. A novel sequence
motif, the S100 protein element, situated in close proximity to the TATA
box of the genes of several members of the S100 protein subfamily, has been
identified. In addition, multiple repeats with similar nucleotide sequence
and location to the recently reported beta globin direct repeat elements
have been also found in the human S100 beta promoter. A full length (17.3
kilobases) copy of the human S100 beta gene was constructed and transfected
into rat glioma C6 cells. Stable transfectants were shown to express
correctly initiated transcripts of the human S100 beta gene, indicating
that the cloned sequences contain functional regulatory transcription
elements.
Cloning and expression of the human S100 beta gene
Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada.
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