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Chromatin remodeling by nuclear receptors
Pratibha B Hebbar1, Trevor K Archer
1Chromatin and Gene Expression Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Science, 111 Alexander Drive, MD-E4-06, PO Box 12233, Research Triangle Park, NC 27709, USA.
Chromosoma
|May 14, 2003
Summary
Nuclear receptors (NRs) access repressed chromatin, recruiting remodeling proteins to activate gene expression. This mechanism, exemplified by glucocorticoid receptor and mouse mammary tumor virus (MMTV) promoter, informs gene regulation in spermatogenesis.
Area of Science:
- Molecular Biology
- Epigenetics
- Gene Regulation
Background:
- Eukaryotic genomes are organized into chromatin, where nucleosomes regulate gene expression by controlling factor accessibility.
- Repressive chromatin structures often hinder transcription factor binding to promoters.
- Nuclear receptors (NRs) are unique transcription factors capable of accessing binding sites within repressive chromatin.
Purpose of the Study:
- To review the role of nuclear receptors (NRs) in recruiting chromatin-modifying enzymes.
- To utilize the glucocorticoid receptor-mediated transactivation of the mouse mammary tumor virus (MMTV) promoter as a model system.
- To explore the impact of chromatin modifications on gene expression during spermatogenesis.
Main Methods:
- Review of existing literature on nuclear receptor function and chromatin remodeling.
- Detailed analysis of the glucocorticoid receptor-mediated transactivation of the MMTV promoter.
- Application of findings from the model system to understand spermatogenesis gene expression.
Main Results:
- Nuclear receptors bind to their sites and recruit ATP-dependent chromatin-remodeling complexes and histone-modifying enzymes.
- This recruitment leads to transcriptional activation from previously repressed chromatin.
- The MMTV promoter model effectively illustrates NR-mediated chromatin modification and gene activation.
Conclusions:
- Nuclear receptors play a critical role in overcoming chromatin-mediated repression to activate gene transcription.
- The mechanisms governing NR recruitment of chromatin modifiers are conserved and applicable to various biological processes.
- Understanding these chromatin dynamics is essential for deciphering gene expression regulation, particularly during complex processes like spermatogenesis.