| First Author | Belikov S | Year | 2009 |
| Journal | Mol Cell Biol | Volume | 29 |
| Issue | 20 | Pages | 5413-25 |
| PubMed ID | 19687299 | Mgi Jnum | J:153898 |
| Mgi Id | MGI:4366590 | Doi | 10.1128/MCB.00368-09 |
| Citation | Belikov S, et al. (2009) FoxA1 binding directs chromatin structure and the functional response of a glucocorticoid receptor-regulated promoter. Mol Cell Biol 29(20):5413-25 |
| abstractText | Reconstitution of the glucocorticoid receptor (GR)-regulated mouse mammary tumor virus (MMTV) promoter in Xenopus oocytes was used to monitor the effects of different transcription factor contexts. Three constitutively binding factors, nuclear factor 1 (NF1), octamer transcription factor 1 (Oct1), and the Forkhead box A1 (FoxA1), were shown to act in concert, to direct the chromatin structure, and to enhance the GR response. FoxA1 has a dominant effect in the absence of hormone and induces a cluster of DNase I-hypersensitive sites in the segment comprising bp -400 to +25. This FoxA1-mediated chromatin remodeling does not induce MMTV transcription, as opposed to that of the GR. However, the robust FoxA1-dependent chromatin opening has the following drastic functional consequences on the hormone regulation: (i) GR-DNA binding is facilitated, as revealed by dimethyl sulfate in vivo footprinting, leading to increased hormone-induced transcription, and (ii) the GR antagonist RU486 is converted into a partial agonist in the presence of FoxA1 via ligand-independent GR activation. We conclude that FoxA1 mediates a preset chromatin structure and directs a context-specific response of a nuclear receptor. Furthermore, the alternative nucleosome arrangement induced by GR and FoxA1 implies this to be determined by constitutive binding of transcription factors rather than by the DNA sequence itself. |
