Estrogen Receptor-α Directs Ordered, Cyclical, and Combinatorial Recruitment of Cofactors on a Natural Target Promoter
Open accessAbstract
Transcriptional activation of a gene involves an orchestrated recruitment of components of the basal transcription machinery and intermediate factors, concomitant with an alteration in local chromatin structure generated by posttranslational modifications of histone tails and nucleosome remodeling. We provide here a comprehensive picture of events resulting in transcriptional activation of a gene, through evaluating the estrogen receptor-alpha (NR3A1) target pS2 gene promoter in MCF-7 cells. This description integrates chromatin remodeling with a kinetic evaluation of cyclical networks of association of 46 transcription factors with the promoter, as determined by chromatin immunoprecipitation assays. We define the concept of a "transcriptional clock" that directs and achieves the sequential and combinatorial assembly of a transcriptionally productive complex on a promoter. Furthermore, the unanticipated findings of key roles for histone deacetylases and nucleosome-remodeling complexes in limiting transcription implies that transcriptional activation is a cyclical process that requires both activating and repressive epigenetic processes.
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A fine-grained time-course experiment following oestrogen receptor activation in a cancer cell line detected multiple waves of progressive recruitment of at least 46 sequence-specific transcription factors and cofactors, eventually resulting in derepression of the oestrogen-response gene pS2.
“This study detected multiple “waves” of a progressive recruitment of at least 46 sequence-specific TFs and cofactors, including chromatin remodelling complexes and histone acetyl-transferases, eventually resulting in a derepression of an oestrogen-response gene pS2 [87].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [87]
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- Authors
- Métivier, R., Penot, G., Hübner, M. R., Reid, G., Brand, H., Koš, M., & Gannon, F.
- Affiliations
- European Molecular Biology Laboratory (DE)
- Corresponding author
- Métivier, Raphaël
- Gannon, Frank
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2003-12
- Volume
- 115
- Issue
- 6
- Pages
- 751-763
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2038208040
- Cited by
- 1,431
- References
- 2
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 14 · 2023: 18 · 2022: 18 · 2021: 29 · 2020: 15 · 2019: 24 · 2018: 38 · 2017: 36 · 2016: 52 · 2015: 60 · 2014: 61 · 2013: 72 · 2012: 79
- FWCI
- 36.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- estrogen receptor alpha, transcriptional activation, cofactor recruitment, chromatin remodeling, histone deacetylase, histone modifications, transcriptional regulatory networks, MCF-7 cells, epigenetic regulation, chromatin structure
- MeSH terms
- Trefoil Factor-1, Biological Clocks, Estrogens, Histone Deacetylases, Humans, Nucleosomes, Promoter Regions, Genetic, Proteins, Receptors, Estrogen, Transcriptional Activation, Tumor Suppressor Proteins, Epigenesis, Genetic, Cell Line, Tumor, Estrogen Receptor alpha
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