Epigenetic mechanisms underlie the crosstalk between growth factors and a steroid hormone
| Autor: | Animesh Chowdhury, Moshe Szyf, Matthew Suderman, Swati Srivastava, Moshit Lindzen, Cindy Körner, Moshe Oren, Stefan Wiemann, Kirti Shukla, Noa Furth, Yehoshua Enuka, Yoav Zaltsman, Mattia Lauriola, Renaud Massart, Yosef Yarden, Morris E. Feldman, Aldema Sas-Chen, Chiara A. Mazza, David Cheishvili |
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| Přispěvatelé: | Enuka, Yehoshua, Feldman, Morris E, Chowdhury, Animesh, Srivastava, Swati, Lindzen, Moshit, Sas-Chen, Aldema, Massart, Renaud, Cheishvili, David, Suderman, Matthew J, Zaltsman, Yoav, Mazza, Chiara A, Shukla, Kirti, Körner, Cindy, Furth, Noa, Lauriola, Mattia, Oren, Moshe, Wiemann, Stefan, Szyf, Moshe, Yarden, Yosef |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Transcription Factor RNA polymerase II Dexamethasone Cell Line Epigenesis Genetic 03 medical and health sciences Glucocorticoid 0302 clinical medicine Cell Movement Genetics Humans Epigenetics Promoter Regions Genetic Enhancer Glucocorticoids Transcription factor Epidermal Growth Factor biology Gene regulation Chromatin and Epigenetics NF-kappa B Promoter DNA Methylation Cell biology Chromatin Crosstalk (biology) 030104 developmental biology Gene Expression Regulation DNA methylation biology.protein RNA Polymerase II Tumor Suppressor Protein p53 Protein Processing Post-Translational 030217 neurology & neurosurgery Transcription Factors Human |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| DOI: | 10.1093/nar/gkx865 |
| Popis: | Crosstalk between growth factors (GFs) and steroid hormones recurs in embryogenesis and is co-opted in pathology, but underlying mechanisms remain elusive. Our data from mammary cells imply that the crosstalk between the epidermal GF and glucocorticoids (GCs) involves transcription factors like p53 and NF-κB, along with reduced pausing and traveling of RNA polymerase II (RNAPII) at both promoters and bodies of GF-inducible genes. Essentially, GCs inhibit positive feedback loops activated by GFs and stimulate the reciprocal inhibitory loops. As expected, no alterations in DNA methylation accompany the transcriptional events instigated by either stimulus, but forced demethylation of regulatory regions broadened the repertoire of GF-inducible genes. We report that enhancers, like some promoters, are poised for activation by GFs and GCs. In addition, within the cooperative interface of the crosstalk, GFs enhance binding of the GC receptor to DNA and, in synergy with GCs, promote productive RNAPII elongation. Reciprocally, within the antagonistic interface GFs hyper-acetylate chromatin at unmethylated promoters and enhancers of genes involved in motility, but GCs hypoacetylate the corresponding regions. In conclusion, unmethylated genomic regions that encode feedback regulatory modules and differentially recruit RNAPII and acetylases/deacetylases underlie the crosstalk between GFs and a steroid hormone. |
| Databáze: | OpenAIRE |
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