Role of the histone chaperone Rtt106 in transcription elongation, chromatin dynamics and regulation of cryptic site transcription

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Gene expression is a key mechanism involved in the control of cellular processes (growth, differentiation and death). A defect in the regulation of gene expression can have dramatic consequences such as failure in cell cycle control, leading to cancer. To understand how transcription works one must consider that eukaryotic DNA is packaged into a condensed structure called chromatin. In addition to a structural role, chromatin represses different step of transcription. We are interested by chromatin dynamics associated to the elongation of transcription. It seems that a defect in this step affects the cellular homeostasis and result in various diseases including myeloid leukemia, Cockayne syndrome and the familial cancer predisposition syndrome von Hippel-Lindau disease. It is not clear of how elongation contribute to these diseases. In order to gain more insights about these diseases, we are interested by chromatin dynamics associated to transcription elongation. To study transcription elongation, we decided to use a very powerful model organism that is the yeast Saccharomyces cerevisiae. Importantly, transcription mechanisms are well conserved throughout the evolution scale and major discoveries in this research field were made using this organism. We will combine genetic, biochemical and genomic approaches to understand how transcription elongation deals with chromatin structure. We will specifically study the protein machines that remodel and assemble chromatin during transcription. These studies will result in better understanding of elongation and may therefore lead to envision new therapies.