PUTATIVE MDR-ENHANCER IS LOCATED ON HUMAN-CHROMOSOME-20 AND NOT LINKED TO THE MDRI GENE ON CHROMOSOME-7

The physiologic expression of the human multidrug resistance MDR1 gene product P-glycoprotein is controlled in a tissue- and cell-specific m anner, but the regulatory mechanisms have not been characterized in gr eat detail. Studies by Kohno et al. [(1990) Biol Chem 265: 19690-19696 ] suggested that a tissue-specific enhancer element located approximat ely 10 kb upstream from the major MDR I transcription start site may a ct to increase the levels of transcription in cultured adrenal and kid ney cells. Using this putative ''MDR enhancer'' as a probe, we isolate d a 14 kb DNA fragment from a genomic DNA library prepared from human fetal liver. The restriction map and partial nucleotide sequence of th is DNA fragment were consistent with the previously described data obt ained for a similar piece of genomic DNA derived from human placenta b y Kohno et al. (ibid.). pulsed-field gel electrophoresis of large geno mic DNA fragments, however, showed that the DNA sequences, including t he putative ''MDR enhancer,'' were not linked to the MDR1 gene. Fluore scence in situ hybridization analysis revealed that this enhancer-like element is located on chromosome 20 at band q13.1 and is, therefore, distinct from the MDR locus on chromosome 7, band q21.1. Thus, this pu tative regulatory element does not modulate the tissue specificity of expression of the MDR1 gene in vivo, but may play a role in the regula tion of expression of another, so far unknown gene. Genes Chromosom Ca ncer 10:267-274 (1994). (C) 1994 Wiley-Liss, Inc.