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Nuclear hormone receptors and gene expression.
1Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Madrid, Spain. aaranda@iib.uam.es
Physiological Reviews
|June 28, 2001
Summary
Nuclear hormone receptors, including those for steroid hormones and vitamin D, regulate gene expression. Ligand binding triggers conformational changes, recruiting coactivators or corepressors to control transcription via chromatin remodeling.
Area of Science:
- Molecular Biology
- Endocrinology
- Genetics
Background:
- The nuclear hormone receptor superfamily encompasses receptors for steroid hormones, thyroid hormones, retinoids, and vitamin D.
- Some "orphan" receptors, previously of unknown ligand, are now known to bind lipid metabolites, regulating gene expression.
Purpose of the Study:
- To elucidate the general molecular mechanism by which nuclear receptors mediate transcriptional responses.
- To understand the role of coregulators in nuclear receptor-mediated gene regulation.
Main Methods:
- The study reviews the known mechanisms of nuclear receptor function, including ligand binding, DNA interaction, and coregulator recruitment.
- It discusses the roles of corepressor and coactivator complexes in modulating chromatin structure and transcriptional activity.
Main Results:
- Nuclear receptors function as ligand-inducible transcription factors, interacting with DNA response elements directly or as dimers.
- Ligand binding induces conformational changes, leading to the recruitment of either corepressor complexes (with histone deacetylase activity) or coactivator complexes (involved in chromatin remodeling and transcription initiation).
Conclusions:
- A general molecular mechanism for nuclear receptor-mediated transcription has been established, involving ligand-dependent recruitment of coregulators.
- This mechanism explains how diverse nuclear receptors regulate target gene expression through chromatin modification and interaction with the transcriptional machinery.