Mechanisms of Olfactory sensory neuron class maintenance in Drosophila : It is all about design and equilibrium

......................................................................................................................... 1 List of papers .................................................................................................................. 3 Abbreviations ................................................................................................................. 4 Introduction ................................................................................................................... 5 Cell, genome and gene regulation ......................................................................... 5 Gene expression regulation .................................................................................... 6 Transcription factors .............................................................................................. 8 DNA binding motifs .............................................................................................. 10 Combinatorial interactions of TFs ...................................................................... 11 Cis-regulatory modules......................................................................................... 12 Promoters, Enhancers/Silencers and Insulators ................................................ 13 Binary vs rheostat regulation of gene expression .............................................. 14 Limits of Combinatorial regulation .................................................................... 15 Epigenetic mechanisms ........................................................................................ 16 Effects and functions of histone modifications and epigenetic codes ............... 18 Whole genome regulation and nucleus localization of expressing genes ......... 19 Neuronal specification .......................................................................................... 21 Generating neuronal diversity ............................................................................. 22 Olfactory system .................................................................................................... 24 Drosophila olfactory system ................................................................................ 24 Odorant receptors ................................................................................................. 28 Drosophila Odorant receptors ............................................................................. 31 Terminal selector genes ........................................................................................ 33 Gene Expression Robustness to environmental changes .................................. 33 Aims .............................................................................................................................. 37 Materials and methods ................................................................................................ 39 The Gal4/UAS/TARGET system ......................................................................... 39 OR markers ........................................................................................................... 39 RNAi methodology and Reverse genetic screening ........................................... 40 Electrophoretic Mobility Shift Assay .................................................................. 41 Results ........................................................................................................................... 45 Paper I .................................................................................................................... 45 Principal findings ............................................................................................ 45 Paper II .................................................................................................................. 47 Principal findings ............................................................................................ 47 Paper III ................................................................................................................. 49 Principal findings ............................................................................................ 49 Discussion ..................................................................................................................... 51 OSN class specification and maintenance ........................................................... 51 Repression modulates OR expression ................................................................. 53 Interacting subnetworks specify OSN classes .................................................... 54 OR genes promoters are enhansosomes .............................................................. 56 Low-affinity motifs can be advantageous for gene regulation ......................... 57 Change in the TF composition of a cell can reprogram an adult cell to a new fate .......................................................................................................................... 58 Modern environments and Human diseases ...................................................... 61 Popular science abstract ............................................................................................. 62 How our neurons are doing what they should do? ............................................ 62 Acknowledgements ...................................................................................................... 64 References ..................................................................................................................... 67