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Originally published In Press as doi:10.1074/jbc.M104723200 on July 6, 2001
J. Biol. Chem., Vol. 276, Issue 38, 35405-35413, September 21, 2001
Differential Cooperation between Regulatory Sequences
Required for Human CD53 Gene Expression*
Javier
Hernández-Torres,
Mónica
Yunta , and
Pedro A.
Lazo§
From the Centro de Investigación del Cáncer, Instituto
de Biología Molecular y Celular del Cáncer, Consejo
Superior de Investigaciones Científicas, Universidad de
Salamanca, Campus Miguel de Unamuno, E-37007 Salamanca, Spain and the
Unidad de Genética y Medicina Molecular, Centro Nacional de
Biología Fundamental, Instituto de Salud Carlos III,
E-28220 Majadahonda, Spain
CD53 is a tetraspanin protein mostly expressed in
to the lymphoid-myeloid lineage. We have characterized the human
CD53 gene regulatory region. Within the proximal 2 kilobases, and with opposite transcriptional orientation, is located
the promoter-enhancer of a second gene, which does not affect
CD53. Twenty-four copies of a CA dinucleotide repeat
separate these two gene promoters. The proximal enhanceosome of the
human CD53 gene is comprised between residues 266 and
+84, and can be subdivided into four major subregions, two of them
within exon 1. Mutational analysis identified several cooperating
sequences. An Sp1 and an ets-1 site, at positions 115 and +62,
respectively, are essential for transcriptional competence in all cell
lines. Five other regulatory sequences have a dual role, activator or
down-regulator, depending on the cell line. At the end of the
non-coding exon 1, +64 to +83, there is a second ets-1 regulatory
element, which is required for high level of transcription, in
cooperation with the Sp1 site, in K562 and Molt-4, but not in Namalwa
cells, where it functions as a repressor. This Sp1 site also cooperates
with another ets-1/PU.1 site at 172. Different cell types use
different regulatory sequences in the enhanceosome for the expression
of the same gene.
*
This work was supported in part by Ministerio de Ciencia y
Tecnología Grant SAF2000/0169 and Junta de Castilla y
León Grant CSI-1/01.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AJ243474.
Supported by a fellowship from the Instituto de Salud Carlos III.
§
To whom correspondence should be addressed: Centro de
Investigación del Cáncer, CSIC-Universidad de Salamanca,
Campus Miguel de Unamuno, E-37007 Salamanca, Spain. Tel.:
34-923-294-804; Fax: 34-923-294-795; E-mail: plazozbi@usal.es.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.

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