Linked Life Data

21527503

Source:http://linkedlifedata.com/resource/pubmed/id/21527503

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2011-5-23
pubmed:abstractText
Differentiated HC-11 cells ectopically expressing progesterone receptor (PR) were used to explore the molecular mechanisms by which progesterone suppresses ?-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 ?-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 ?-casein gene. Recruitment of signal transducer and activator of transcription 5a, glucocorticoid receptor, and the CCAAT enhancer binding protein ? to the enhancer and proximal promoter of ?-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 ?-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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1944-9917
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
955-68
pubmed:meshHeading
pubmed-meshheading:21527503-Animals, pubmed-meshheading:21527503-Caseins, pubmed-meshheading:21527503-Cell Line, pubmed-meshheading:21527503-Chromatin, pubmed-meshheading:21527503-Enhancer Elements, Genetic, pubmed-meshheading:21527503-Epithelial Cells, pubmed-meshheading:21527503-Female, pubmed-meshheading:21527503-Gene Expression Regulation, pubmed-meshheading:21527503-Humans, pubmed-meshheading:21527503-Hydrocortisone, pubmed-meshheading:21527503-Mammary Glands, Animal, pubmed-meshheading:21527503-Mice, pubmed-meshheading:21527503-Progestins, pubmed-meshheading:21527503-Prolactin, pubmed-meshheading:21527503-Promegestone, pubmed-meshheading:21527503-Promoter Regions, Genetic, pubmed-meshheading:21527503-Protein Multimerization, pubmed-meshheading:21527503-Receptors, Glucocorticoid, pubmed-meshheading:21527503-Receptors, Progesterone, pubmed-meshheading:21527503-STAT5 Transcription Factor, pubmed-meshheading:21527503-Transcription, Genetic, pubmed-meshheading:21527503-Transcriptional Activation
pubmed:year
2011
pubmed:articleTitle
Progesterone receptor directly inhibits ?-casein gene transcription in mammary epithelial cells through promoting promoter and enhancer repressive chromatin modifications.
pubmed:affiliation
Baylor College of Medicine, Department of Molecular and Cellular Biology, Houston, Texas 77030, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural