c-Myb and Members of the c-Ets Family of Transcription Factors Act as Molecular Switches to Mediate Opposite Steroid Regulation of the Human Glucocorticoid Receptor 1A Promoter
| Autor: | Wayne V. Vedeckis, Chuan Dong Geng |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Chromatin Immunoprecipitation
T-Lymphocytes Blotting Western Apoptosis Biology Transfection Models Biological Polymerase Chain Reaction complex mixtures Biochemistry Jurkat cells Cell Line Proto-Oncogene Protein c-ets-2 Proto-Oncogene Protein c-ets-1 Jurkat Cells Proto-Oncogene Proteins c-myb chemistry.chemical_compound Receptors Glucocorticoid Glucocorticoid receptor Proto-Oncogene Proteins Humans Cell Lineage MYB Lymphocytes Luciferases Promoter Regions Genetic Molecular Biology Transcription factor Genes Dominant B-Lymphocytes Reporter gene Leukemia Proto-Oncogene Proteins c-ets Lymphoblast Exons Cell Biology Molecular biology Protein Structure Tertiary Up-Regulation DNA-Binding Proteins Electroporation Gene Expression Regulation chemistry Trans-Activators Steroids Chromatin immunoprecipitation DNA Protein Binding Transcription Factors |
| Zdroj: | Journal of Biological Chemistry. 280:43264-43271 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m508245200 |
| Popis: | Steroid auto-regulation of the human glucocorticoid receptor (hGR) 1A promoter in lymphoblast cells resides largely in two DNA elements (footprints 11 and 12). We show here that c-Myb and c-Ets family members (Ets-1/2, PU.1, and Spi-B) control hGR 1A promoter regulation in T- and B-lymphoblast cells. Two T-lymphoblast lines, CEM-C7 and Jurkat, contain high levels of c-Myb and low levels of PU.1, whereas the opposite is true in IM-9 B-lymphoblasts. In Jurkat cells, overexpression of c-Ets-1, c-Ets-2, or PU.1 effectively represses dexamethasone-mediated up-regulation of an hGR 1A promoter-luciferase reporter gene, as do dominant negative c-Myb (c-Myb DNA-binding domain) or Ets proteins (Ets-2 DNA-binding domain). Overexpression of c-Myb in IM-9 cells confers hormone-dependent up-regulation to the hGR 1A promoter reporter gene. Chromatin immunoprecipitation assays show that hormone treatment causes the recruitment of hGR and c-Myb to the hGR 1A promoter in CEM-C7 cells, whereas hGR and PU.1 are recruited to this promoter in IM-9 cells. These observations suggest that the specific transcription factor that binds to footprint 12, when hGR binds to the adjacent footprint 11, determines the direction of hGR 1A promoter auto-regulation. This leads to a "molecular switch" model for auto-regulation of the hGR 1A promoter. |
| Databáze: | OpenAIRE |
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