ArticleMolecular endocrinology (Baltimore, Md.)2011
Progesterone receptor directly inhibits β-casein gene transcription in mammary epithelial cells through promoting promoter and enhancer repressive chromatin modifications.
Article in Molecular endocrinology (Baltimore, Md.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- Mutation of Signal Transducer and Activator of Transcription 5 (STAT5) Binding Sites Decreases Milk Allergen αFoods (Basel, Switzerland) · 2022Article
- Nuclear Receptors in Ovarian Function.Advances in experimental medicine and biology · 2022Article
- Redundant and non-redundant cytokine-activated enhancers control Csn1s2b expression in the lactating mouse mammary gland.Nature communications · 2021Article
- Reciprocal fine-tuning of progesterone and prolactin-regulated gene expression in breast cancer cells.Molecular and cellular endocrinology · 2020Article
- The glucocorticoid receptor interferes with progesterone receptor-dependent genomic regulation in breast cancer cells.Nucleic acids research · 2019Article
- Steroid hormone receptors silence genes by a chromatin-targeted mechanism similar to those used for gene activation.Transcription · 2017Article
- Regeneration of Bovine Mammary Gland in Immunodeficient Mice by Transplantation of Bovine Mammary Epithelial Cells Mixed with Matrigel.International journal of stem cells · 2016Article
- Cyclin A2 and its associated kinase activity are required for optimal induction of progesterone receptor target genes in breast cancer cells.The Journal of steroid biochemistry and molecular biology · 2014Article
- Buffalo alpha S1-casein gene 5'-flanking region and its interspecies comparison.Journal of applied genetics · 2014Article
- DNA methylation and transcription in a distal region upstream from the bovine AlphaS1 casein gene after once or twice daily milking.PloS one · 2014Article
- Underlying mechanisms involved in the decrease of milk secretion during Escherichia coli endotoxin induced mastitis in lactating mice.Veterinary research · 2013Article
- Progesterone receptor and Stat5 signaling cross talk through RANKL in mammary epithelial cells.Molecular endocrinology (Baltimore, Md.) · 2013Article
- The requirement for p42/p44 MAPK activity in progesterone receptor-mediated gene regulation is target gene-specific.Steroids · 2013Article
- Hormone-sensing cells require Wip1 for paracrine stimulation in normal and premalignant mammary epithelium.Breast cancer research : BCR · 2013Article
- The biology of progesterone receptor in the normal mammary gland and in breast cancer.Molecular and cellular endocrinology · 2012Review
- The chromatin landscape of the casein gene locus.Hormone molecular biology and clinical investigation · 2012Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Differentiated HC-11 cells ectopically expressing progesterone receptor (PR) were used to explore the molecular mechanisms by which progesterone suppresses β-casein gene transcription induced by prolactin (PRL) and glucocorticoids in the mammary gland. As detected by chromatin immunoprecipitation assays, treatment of cells with the progestin agonist R5020 induced a rapid recruitment (5 min) of PR to the proximal promoter (-235 bp) and distal enhancer (-6 kb upstream of transcription start site) of β-casein. PR remained bound for 4 h and was dissociated by 24 h after treatment. Despite efficient binding, the hormone agonist-occupied PR did not stimulate transcription of the β-casein gene. Recruitment of signal transducer and activator of transcription 5a, glucocorticoid receptor, and the CCAAT enhancer binding protein β to the enhancer and proximal promoter of β-casein induced by PRL and glucocorticoids was blocked by progestin cotreatment, whereas PR binding was induced under these conditions. PRL/glucocorticoid-induced histone acetylation and the recruitment of the coactivator p300 and RNA polymerase II required for gene activation were also inhibited by progestin. In addition, progestin prevented dissociation of the corepressors Yin and Yang 1 and histone deacetylase 3 from the promoter, and demethylation of lysine 9 of histone 3 induced by PRL and glucocorticoids. These studies are consistent with the conclusion that progesterone interferes with PRL/glucocorticoid induction of β-casein transcription by a physical interaction of PR with the promoter and enhancer that blocks assembly of a transcriptional activation complex and dissociation of corepressors and promotes repressive chromatin modifications. These studies define a novel mechanism of steroid receptor-mediated transcriptional repression of a physiologically important gene in mammary gland development and differentiation.
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