Identification and Characterization of Enhancers Controlling the Inflammatory Gene Expression Program in Macrophages
| Autor: | Adeline Chew, Francesca De Santa, Gioacchino Natoli, Chia-Lin Wei, Flore Mietton, Lorne Lonie, Serena Ghisletti, Iros Barozzi, Lorna Gregory, Jiannis Ragoussis, Sara Polletti, Elisa Venturini |
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| Rok vydání: | 2010 |
| Předmět: |
Lipopolysaccharides
Immunology Enhancer RNAs Regulatory Sequences Nucleic Acid Biology Mice 03 medical and health sciences 0302 clinical medicine Proto-Oncogene Proteins Gene expression Animals Immunology and Allergy MOLIMMUNO Enhancer Transcription factor Cells Cultured 030304 developmental biology Inflammation Regulation of gene expression Genetics 0303 health sciences SYSBIO Binding Sites Activator (genetics) Gene Expression Profiling Macrophages Chromatin Cell biology Infectious Diseases Gene Expression Regulation Regulatory sequence Trans-Activators Female Ectopic expression E1A-Associated p300 Protein 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | Immunity. 32:317-328 |
| ISSN: | 1074-7613 |
| Popis: | SummaryEnhancers determine tissue-specific gene expression programs. Enhancers are marked by high histone H3 lysine 4 mono-methylation (H3K4me1) and by the acetyl-transferase p300, which has allowed genome-wide enhancer identification. However, the regulatory principles by which subsets of enhancers become active in specific developmental and/or environmental contexts are unknown. We exploited inducible p300 binding to chromatin to identify, and then mechanistically dissect, enhancers controlling endotoxin-stimulated gene expression in macrophages. In these enhancers, binding sites for the lineage-restricted and constitutive Ets protein PU.1 coexisted with those for ubiquitous stress-inducible transcription factors such as NF-κB, IRF, and AP-1. PU.1 was required for maintaining H3K4me1 at macrophage-specific enhancers. Reciprocally, ectopic expression of PU.1 reactivated these enhancers in fibroblasts. Thus, the combinatorial assembly of tissue- and signal-specific transcription factors determines the activity of a distinct group of enhancers. We suggest that this may represent a general paradigm in tissue-restricted and stimulus-responsive gene regulation. |
| Databáze: | OpenAIRE |
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