Putative “MDR enhancer” is located on human chromosome 20 and not linked to the MDRI gene on chromosome 7

Ursula A. Germann, Patricia V Schoenlein, Drazen B. Zimonjic, Nicholas C. Popescu, Ira Pastan, Michael M. Gottesman

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)267-274
Number of pages8
JournalGenes, Chromosomes and Cancer
Volume10
Issue number4
DOIs
StatePublished - Jan 1 1994

Fingerprint

Chromosomes, Human, Pair 20
Chromosomes, Human, Pair 7
Human Chromosomes
DNA
Genes
MDR Genes
Organ Specificity
Genomic Library
Neoplasm Genes
Transcription Initiation Site
Fluorescence In Situ Hybridization
Gene Library
Placenta
Electrophoresis
Gels
Kidney
Gene Expression
Liver

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

Cite this

Putative “MDR enhancer” is located on human chromosome 20 and not linked to the MDRI gene on chromosome 7. / Germann, Ursula A.; Schoenlein, Patricia V; Zimonjic, Drazen B.; Popescu, Nicholas C.; Pastan, Ira; Gottesman, Michael M.

In: Genes, Chromosomes and Cancer, Vol. 10, No. 4, 01.01.1994, p. 267-274.

Research output: Contribution to journalArticle

Germann, Ursula A. ; Schoenlein, Patricia V ; Zimonjic, Drazen B. ; Popescu, Nicholas C. ; Pastan, Ira ; Gottesman, Michael M. / Putative “MDR enhancer” is located on human chromosome 20 and not linked to the MDRI gene on chromosome 7. In: Genes, Chromosomes and Cancer. 1994 ; Vol. 10, No. 4. pp. 267-274.
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abstract = "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). {\circledC} 1994 Wiley‐Liss, Inc.",
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