TY - JOUR
T1 - Putative “MDR enhancer” is located on human chromosome 20 and not linked to the MDRI gene on chromosome 7
AU - Germann, Ursula A.
AU - Schoenlein, Patricia V.
AU - Zimonjic, Drazen B.
AU - Popescu, Nicholas C.
AU - Pastan, Ira
AU - Gottesman, Michael M.
PY - 1994/8
Y1 - 1994/8
N2 - The physiologic expression of the human multidrug resistance MDRI gene product P‐glycoprotein is controlled in a tissue‐ and cell‐specific manner, but the regulatory mechanisms have not been characterized in great detail. Studies by Kohno et al. [(1990) J Biol Chem 265:19690–19696] suggested that a tissue‐specific enhancer element located approximately 10 kb upstream from the major MDRI transcription start site may act to increase the levels of transcription in cultured adrenal and kidney cells. Using this putative “MDR enhancer” as a probe, we isolated a 14 kb DNA fragment from a genomic DNA library prepared from human fetal liver. The restriction map and partial nucleotide sequence of this DNA fragment were consistent with the previously described data obtained for a similar piece of genomic DNA derived from human placenta by Kohno et al. (ibid.). Pulsed‐field gel electrophoresis of large genomic DNA fragments, however, showed that the DNA sequences, including the putative “MDR enhancer,” were not linked to the MDRI gene. Fluorescence 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 putative regulatory element does not modulate the tissue specificity of expression of the MDRI gene in vivo, but may play a role in the regulation of expression of another, so far unknown gene. Genes Chromosom Cancer 10:267–274 (1994). © 1994 Wiley‐Liss, Inc.
AB - The physiologic expression of the human multidrug resistance MDRI gene product P‐glycoprotein is controlled in a tissue‐ and cell‐specific manner, but the regulatory mechanisms have not been characterized in great detail. Studies by Kohno et al. [(1990) J Biol Chem 265:19690–19696] suggested that a tissue‐specific enhancer element located approximately 10 kb upstream from the major MDRI transcription start site may act to increase the levels of transcription in cultured adrenal and kidney cells. Using this putative “MDR enhancer” as a probe, we isolated a 14 kb DNA fragment from a genomic DNA library prepared from human fetal liver. The restriction map and partial nucleotide sequence of this DNA fragment were consistent with the previously described data obtained for a similar piece of genomic DNA derived from human placenta by Kohno et al. (ibid.). Pulsed‐field gel electrophoresis of large genomic DNA fragments, however, showed that the DNA sequences, including the putative “MDR enhancer,” were not linked to the MDRI gene. Fluorescence 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 putative regulatory element does not modulate the tissue specificity of expression of the MDRI gene in vivo, but may play a role in the regulation of expression of another, so far unknown gene. Genes Chromosom Cancer 10:267–274 (1994). © 1994 Wiley‐Liss, Inc.
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U2 - 10.1002/gcc.2870100408
DO - 10.1002/gcc.2870100408
M3 - Article
C2 - 7522541
AN - SCOPUS:0028169940
SN - 1045-2257
VL - 10
SP - 267
EP - 274
JO - Genes Chromosomes and Cancer
JF - Genes Chromosomes and Cancer
IS - 4
ER -