Transcription Factor Effects on Chromatin Organisation and Gene Regulation

________________________________________________________ 3 List of publications________________________________________________ 4 Table of contents _________________________________________________ 5 List of abbreviations_______________________________________________ 6 Introduction _____________________________________________________ 7 Chromatin ___________________________________________________________7 The nucleosome ___________________________________________________________ 7 Chromatin remodelling______________________________________________________ 9 Histone modifications, epigenetics ____________________________________________ 10 Histone acetylation _____________________________________________________ 11 Histone methylation_____________________________________________________ 11 Histone ubiquitylation ___________________________________________________ 12 Other modifications _____________________________________________________ 12 Heterochromatin__________________________________________________________ 13 Transcription _______________________________________________________15 The holoenzyme: PIC and mediator ___________________________________________ 15 Gene activation___________________________________________________________ 17 DNA sequence specific transcription factors ____________________________________ 19 Nuclear receptors_______________________________________________________ 20 Fox proteins___________________________________________________________ 21 NF1 and Oct __________________________________________________________ 23 Co-activators ____________________________________________________________ 24 The enhanceosome ________________________________________________________ 24 Chromatin in development_____________________________________________25 MMTV transcription _________________________________________________26 Aims __________________________________________________________ 29 Material and methods_____________________________________________ 30 Xenopus laevis oocytes as a model system _________________________________30 Results and discussion ____________________________________________ 31 Summary of findings _________________________________________________31 NF1 binds to the non-induced MMTV LTR _______________________________32 NF1 and Oct1 cooperate to preset the MMTV LTR nucleosomal array_________32 The MMTV LTR enhanceosome ________________________________________34 Finding and characterisation of novel FoxA sites in the MMTV LTR __________36 FoxA1 effects on MMTV LTR chromatin and enhanceosome structure ________38 FoxA1, NF1 Oct1 and GR interactions ___________________________________39 A role for FoxA, NF1 and Oct in MMTV propagation ______________________40 Future perspectives ______________________________________________ 41 Acknowledgements_______________________________________________ 42 References______________________________________________________ 43