Induction of Progesterone Target Genes Requires Activation of Erk and Msk Kinases and Phosphorylation of Histone H3
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How genes are regulated in the context of chromatin is a central question of biology. Steroid hormones control gene expression via interaction of their receptors with target sequences on DNA but can also activate cytoplasmic signaling cascades. Here we report that rapid Erk activation by progestins participates in induction of target genes by preparing the chromatin for transcription. Five minutes after hormone treatment, Erk activation leads to phosphorylation of the progesterone receptor (PR), activation of Msk1, and recruitment of a complex of the three proteins to a nucleosome on the MMTV promoter. Msk1 phosphorylates histone H3, leading to displacement of HP1gamma and recruitment of Brg1 and RNA polymerase II. Cell-free experiments show a direct interaction between PR, Erk, and Msk1 and support the importance of H3 phosphorylation for nucleosome remodeling. Inhibition of Msk1 activation blocks recruitment of the kinase complex, H3 phosphorylation, and HP1gamma displacement, thus precluding remodeling and induction of the promoter.
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Histone phosphorylation contributes to transcription as a chromatin mark accounting for, in cooperation with other histone modifications, chromatin remodeling and promoter recruitment of RXR/RAR heterodimers and the transcriptional machinery.
“According to several reports ( 96, 142, 143 ), histone phosphorylation would contribute to transcription as a chromatin mark accounting for, in cooperation with other histone modifi cations, chromatin remodeling and promoter recruitment of RXR/RAR heterodimers and the transcriptional machinery ( Fig. 6 ).”
From Vitamin A and retinoid signaling: genomic and nongenomic effects (2013) · cites this paper as [142]
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Self-citation
- Authors
- Vicent, G. P., Ballaré, C., Nacht, A. S., Clausell, J., Subtil-Rodríguez, A., Quiles, I., Jordan, A., & Beato, M.
- Affiliations
- Universitat Pompeu Fabra (ES)
- Corresponding author
- Beato, Miguel
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2006-11
- Volume
- 24
- Issue
- 3
- Pages
- 367-381
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W1974761743
- Cited by
- 223
- References
- 48
- Citations by year
- 2026: 3 · 2024: 4 · 2023: 5 · 2022: 3 · 2021: 5 · 2020: 5 · 2019: 4 · 2018: 4 · 2017: 8 · 2016: 13 · 2015: 8 · 2014: 12 · 2013: 21 · 2012: 17
- FWCI
- 8.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular 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
- progesterone receptor, progestins, ERK activation, histone H3 phosphorylation, chromatin remodeling, nucleosome remodeling, SMARCA4, RNA polymerase II recruitment, MMTV promoter, steroid hormone signaling, transcriptional activation
- MeSH terms
- Animals, Cell-Free System, Chromosomal Proteins, Non-Histone, Enzyme Activation, Enzyme Inhibitors, Histones, Lysine, Mammary Tumor Virus, Mouse, Methylation, Nucleosomes, Phosphorylation, Progestins, Promoter Regions, Genetic, Protein Binding, Receptors, Progesterone, RNA Polymerase II, Serine, Substrate Specificity, Transcription Factors, Tumor Cells, Cultured, Mitogen-Activated Protein Kinase 1, Ribosomal Protein S6 Kinases, 90-kDa, Chromatin Assembly and Disassembly, Mitogen-Activated Protein Kinase 3, Mice
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