Accurate chromatin organization of the mouse mammary tumor virus promoter determines the nature of the synergism between transcription factors.
The mechanism underlying the synergism between transcription factors in eukaryotic gene expression is not fully understood. In minichromosomes assembled in vitro the synergism between steroid hormone receptors (SHRs) and nuclear factor 1 (NF1) on the mouse mammary tumor virus (MMTV) promoter does not require the proline-rich transactivation domain (PRD) of NF1. Here we show that similar results are obtained in yeast. In contrast, replacing the native hormone-responsive elements (HREs) by a single HRE results in a more accessible chromatin and makes the synergism with SHR dependent on the PRD of NF1. Following hormone induction, in addition to glucocorticoid receptor, the DNA binding domain of NF1 is needed and sufficient for establishing an open chromatin conformation on the wild type MMTV promoter. Thus, NF1 acts as a classical transcription factor in a relaxed chromatin context, whereas in the context of the wild type chromatin DNA binding of NF1 is sufficient to cooperate with SHRs by stabilizing an open chromatin conformation.
Prado
Felix
F
Institut für Molekularbiologie und Tumorforschung (IMT), Philipps-Universität, E-Mannkopff-Str. 2, D-35033 Marburg, Germany.
Koop
Ronald
R
Beato
Miguel
M
D000818:Animals; D001665:Binding Sites; D002843:Chromatin / Q000737:chemistry* / Q000378:metabolism*; D002875:Chromosomes / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D009154:Mutation; D025542:Neurofibromin 1 / Q000737:chemistry / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D051381:Rats; D013552:Swine; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D001616:beta-Galactosidase / Q000378:metabolism
D002843:Chromatin; D025542:Neurofibromin 1; D014157:Transcription Factors; D004247:DNA; D003850:Deoxyribonuclease I; D015252:Deoxyribonucleases, Type II Site-Specific; C032229:GANTC-specific type II deoxyribonucleases; D001616:beta-Galactosidase