Détails de la réservation
- Le : 27 October 2017
- De : 10 h 00
- à : 16 h 00
- Salle : Salle de conférence
Détails de l'évènement
Dr. Roberto FERRARI
Center for Genomic Regulation (CRG), Barcelona, Spain
"Serum starvation shifts TFIIIC binding to impact genome structure and function of human cells"
Résumé
Folding of the human genome from a fiber-like structure into a higher-order assembly is absolutely crucial for all nuclear processes1. Different kind of signaling and stress conditions, such as heat shock (HS) or serum starvation (SS) that can certainly impact nuclear functions might also reflect into changes underlining chromatin architecture2. CTCF and TFIIIC are genome insulators conserved from invertebrates to mammals that can act in regulating 3D genome organization3. However, thus far structural studies of genome organization have been primarily focused on the role of CTCF and very little on the interplay between mammalian insulators especially during stress conditions. Here we report that TFIIIC, besides its known role in RNA polymerase III (pol3) transcription, participates in 3D genome reshaping in normal and cancer cells in response to serum deprivation. Remarkably, we uncover a general reversible mechanism by which, following growth factor depletion, TFIIIC shifts its enrichment from tRNA genes to genomic regions harboring acetylated young Short-INterspersed Elements (SINE) close to pol2 promoters. We report that TFIIIC binding to these Alu is required to increase H3 Lysine-18 acetylation (H3K18ac) and establish proper DNA looping via interaction with pre-existing Cohesin and CTCF binding sites in order to sustain expression of a subset of genes that regulate nuclear, cell cycle and growth factor response in a serum-dependent manner. All together these data shed light on the complex role of TFIIIC and transposable elements in regulating gene expression and 3D organization in human, and expose a sophisticated way in which cells can re-utilize a factor of a growth-sensing machinery to rewire gene expression, epigenetic and 3D genome reorganization to communicate changes in nutrients availability.
Invitation: Martin Teichmann – ARNA Inserm U1212; CNRS UMR 5320
Responsable
- Nom : Teichmann Martin