Grant: Project Grant

To respond to a signal a cell modulates the expression of its genes. This is achieved, in general, by the fine-tuning of genes transcription. However, the packaging of DNA into chromatin has profound effects on processes related to DNA, including transcription by RNA polymerase II (RNAP II). Nucleosomes, the basic structural component of chromatin, inhibit RNAP II. Cells adapted a complex mechanism involving many proteins to overcome the nucleosomal obstacle. Chromatin undergoes a conformational change during transcription and this structure is restored to a normal conformation after RNAP II passage. Among other proteins, histone chaperone are able to reassemble nucleosomes in the wake of RNAP II. In their absence, nucleosomes are not refolded properly resulting in nucleosomal loss and a permissive chromatin structure along coding regions with detrimental consequences to the cell. This includes global activation of spurious transcription at a large number of cryptic promoters located within coding regions of genes. In other words, histone chaperones help the cell to focus the transcription machinery on real promoters and inhibit false cryptic promoters. In this proposal, we focus on the understanding of the function of two histone chaperones, Spt2 and Spt6. These factors, protects, rescues and/or recycles old nucleosomes helping the cells to maintain their epigenetic memory.