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The FASEB Journal, Vol 6, 2524-2529, Copyright © 1992 by The Federation of American Societies for Experimental Biology
REVIEWS |
H Gronemeyer
Laboratoire de Genetique Moleculaire des Eucaryotes, CNRS, Unite 184 de Biologie Moleculaire et de Genie, Genetique de l'INSERM, Faculte de Medecine, Strasbourg, France.
Multiple regulatory mechanisms assure that signal transduction, involving the nuclear receptor interface, results in an accurate regulation of the respective gene networks. These mechanisms involve selective expression of the cognate receptor and its binding to specific hormone response elements of target genes. However, superimposed onto this "simple" control of activity is interpretation of the signal by the multiple functional modules of a given receptor, based on a specific interplay with 1) various factors binding to complex target gene promoters, 2) cell-specific transcription factors that mediate its enhancer function, and 3) other signaling pathways. This interpretation can be further modulated by the differential target gene specificities of receptor isoforms and, according to in vitro evidence, by factors that increase the efficiency of the receptor to interact with its response element. Thus, steroid hormone-regulated gene transcription involves a multitude of interactive elements, as is expected from the central role of nuclear receptors in homeostasis, embryonic development, and differentiation.
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