Differential cooperation between regulatory sequences required for human CD53 gene expression.
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.
Hernández-Torres
J
J
Centro de Investigación del Cáncer, Instituto de Biologia Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Cientificas, Universidad de Salamanca, Campus Miguel de Unamuno, E-37007 Salamanca, Spain.
Yunta
M
M
Lazo
P A
PA
D015703:Antigens, CD / Q000235:genetics*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D002675:Child, Preschool; D004247:DNA; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D060265:Tetraspanin 25; D014157:Transcription Factors / Q000378:metabolism
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C554894:CD53 protein, human; D060265:Tetraspanin 25; D014157:Transcription Factors; D004247:DNA