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Nuclear receptor coactivators
C K Glass1, D W Rose, M G Rosenfeld
1Division of Cellular and Molecular Medicine, Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Abstract:
Retinoic acid, steroid and thyroid hormones regulate complex programs of gene expression by binding to intracellular receptors that are members of the nuclear receptor superfamily of ligand-dependent transcription factors. Recent studies have led to the identification and cloning of genes encoding coactivator molecules that appear to play important roles in mediating ligand-dependent transcription by members of this family. The identification of these coactivator molecules suggests a point of entry into the general transcriptional machinery that is common to several other classes of regulated transcription factors.
Insights
Nuclear receptors, like those for retinoic acid, steroid, and thyroid hormones, control gene expression. Newly identified coactivator molecules are crucial for this process, linking receptors to the general transcription machinery.
Area of Science:
- Molecular Biology
- Genetics
- Endocrinology
Background:
- Retinoic acid, steroid, and thyroid hormones are key regulators of gene expression.
- These hormones function via intracellular receptors belonging to the nuclear receptor superfamily.
- Nuclear receptors act as ligand-dependent transcription factors.
Purpose of the Study:
- To investigate the role of coactivator molecules in nuclear receptor-mediated transcription.
- To identify the molecular mechanisms underlying ligand-dependent gene regulation by nuclear receptors.
- To explore the connection between nuclear receptor coactivators and the general transcriptional machinery.
Main Methods:
- Gene cloning and identification of coactivator molecules.
- Analysis of ligand-dependent transcriptional activity.
- Investigating interactions with the general transcription machinery.
Main Results:
- Identification and cloning of novel coactivator molecules.
- Demonstration of the coactivators' essential role in mediating ligand-dependent transcription.
- Evidence suggesting a common entry point into the transcriptional machinery for various transcription factors.
Conclusions:
- Coactivator molecules are critical for nuclear receptor function.
- These coactivators bridge nuclear receptors and the general transcriptional machinery.
- The findings provide insights into a conserved mechanism of gene regulation.