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Nucleosome-driven transcription factor binding and gene regulation
Cecilia Ballaré1, Giancarlo Castellano, Laura Gaveglia
1Gene Regulation Stem Cells and Cancer Program, Centre for Genomic Regulation (CRG), 08003 Barcelona, Spain.
Molecular Cell
|November 27, 2012
Summary
Transcription factors like the progesterone receptor (PR) need nucleosomes for proper binding and function. This study reveals that PR binding sites (PRbs) are crucial for hormonal gene regulation in breast cancer cells.
Area of Science:
- Molecular Biology
- Genomics
- Cancer Research
Background:
- Understanding transcription factor function requires identifying target genes and binding sites.
- The role of chromatin, specifically nucleosomes, in transcription factor binding is not fully understood.
- Current models suggest factors bind to nucleosome-depleted regions like DNaseI-hypersensitive sites (DHS).
Purpose of the Study:
- To investigate the role of nucleosomes in progesterone receptor (PR) binding and function.
- To identify PR binding sites (PRbs) and their genomic characteristics in breast cancer cells.
- To understand how progestin stimulation affects PR binding and gene regulation.
Main Methods:
- Chromatin immunoprecipitation (ChIP) followed by deep sequencing.
- Micrococcal nuclease (MNase) and DNaseI assays with deep sequencing.
- Analysis of PR binding sites (PRbs) and nucleosome occupancy in breast cancer cells.
Main Results:
- Progesterone receptor (PR) requires nucleosomes for optimal binding and function, challenging the dominant view.
- Identified 25,000 PR binding sites (PRbs) in progestin-treated breast cancer cells, often containing TGTYCY motifs.
- Functional PRbs were found in enhancers of progesterone-induced genes, showing high nucleosome occupancy and remodeling upon stimulation.
Conclusions:
- Nucleosomes are essential for progesterone receptor (PR) binding and hormonal gene regulation.
- Progestin stimulation induces nucleosome remodeling at PR binding sites, displacing histones.
- This study redefines the understanding of transcription factor binding in the context of chromatin structure.
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