Isolation and characterization of Drosophila nuclear receptor superfamily members.

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Title Isolation and characterization of Drosophila nuclear receptor superfamily members.
Publication Type dissertation
School or College School of Medicine
Department Human Genetics
Author Fisk, Gregory James
Date 1998-03
Description Pulses of the steroid hormone ecdysone induce changes in gene expression that lead to the onset of metamorphosis in Drosophila melanogaster. The large number of nuclear receptor superfamily members that are regulated by ecdysone, as well as the functional interactions among vertebrate members of this superfamily, suggest that combinations of nuclear receptors may dictate tissue- and stage-specific responses to ecdysone. To understand how nuclear receptors may function together during the onset of metamorphosis, all of the superfamily members expressed at this stage must first be identified. As a step toward this goal, an extensive molecular screen was conducted to identify new members of the nuclear receptor superfamily that are expressed during the onset of Drosophila metamorphosis. Three novel genes identified in this manner, DHR38, DHR78, and DHR96, are true members of the nuclear receptor superfamily. DHR38 is the Drosophila homolog of the vertebrate NGFI-B receptor. Analysis of the DNA-binding specificities of DHR78 and DHR96 reveals that these proteins bind to distinct subsets of ecdysone receptor binding sites in vitro. This suggests that these receptors may function together with the ecdysone receptor at the top of the ecdysone-induced regulatory hierarchies. To test this hypothesis, a genetic analysis of DHR78 was conducted. Loss-of-function mutations in DHR78 cause lethality during the third larval instar, prior to the onset of metamorphosis. Genes normally induced by ecdysone during the third larval instar show little or no expression in DHR78 mutants. Localization of DHR78 protein on salivary gland polytene chromosomes demonstrated that this protein binds to a subset of ecdysone receptor binding sites in vivo, including most of the known ecdysone-regulated puff loci. In addition, the lack of phenotypes from ectopic expression of DHR78 suggests that this receptor is regulated posttranslationally. Together, these data suggest that DHR78 is a novel ligand-activated receptor that functions as a critical regulator of ecdysone responses during Drosophila development.
Type Text
Publisher University of Utah
Subject Genetics; Development
Subject MESH Drosophila melanogaster; Ecdysone
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "Isolation and characterization of Drosophila nuclear receptor superfamily members." Spencer S. Eccles Health Sciences Library. Print version of "Isolation and characterization of Drosophila nuclear receptor superfamily members." available at J. Willard Marriott Library Special Collection. QL3.5 1998 .F57.
Rights Management © Gregory James Fisk.
Format application/pdf
Format Medium application/pdf
Identifier us-etd2,22329
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
ARK ark:/87278/s6br96v9
Setname ir_etd
ID 194139
Reference URL https://collections.lib.utah.edu/ark:/87278/s6br96v9
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