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Papers In Press, published online ahead of print July 6, 2001
Centro de Investigacion del Cancer, CSIC-Universidad de Salamanca, Salamanca, Salamanca E-37007
Corresponding Author: plazozbi{at}usal.es
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 to +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. Other five 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.
J. Biol. Chem, 10.1074/jbc.M104723200
Submitted on May 23, 2001
Revised on July 5, 2001
Accepted on July 5, 2001
Differential cooperation between regulatory sequences required for human CD53 gene expression
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