BN Talk - Francesca Mattiroli (candidate ND Lab): 'Evolution and assembly of eukaryotic chromatin'



13:00 hrs


A1.100, TU Delft


Nucleosomes composition and dynamics are key determinants of DNA accessibility, and profoundly affect transcription, replication and DNA repair in all eukaryotes. The seminar will focus on two aspects of nucleosome biology.

The first part will discuss the evolution of eukaryotic chromatin structure. We solved the crystal structure of histone-based archaeal chromatin. Archaeal chromatin has the capacity to polymerize in a way that structurally resembles a continuous nucleosomal ramp. Using a combination of in vitro and in vivo techniques, our work shows how the structural organization of DNA-histone complexes preceded the discrete assembly of eukaryotic chromatin into octameric units, with important implications for our understanding of how genome organization has evolved.

  • The second part of the talk focuses on the mechanism of eukaryotic nucleosome assembly coupled to DNA replication, a key process that regulates cell identity and survival. Chromatin assembly factor 1 (CAF-1) is a H3-H4 histone chaperone that associates with the replisome and orchestrates chromatin assembly following DNA synthesis. Here we elucidate the CAF-1H3-H4 binding mode and the mechanism of nucleosome assembly. Our data reveals an elegant activation mechanism that functionally couples histone and DNA binding. This drives the formation of a transient CAF-1histoneDNA intermediate containing two CAF-1 complexes, each associated with one H3-H4 dimer. Here, the (H3-H4)2 tetramer is formed and deposited onto DNA. Our work provides the first direct mechanism for histone deposition by a histone chaperone and advances our understanding of the mechanisms regulating epigenome inheritance through DNA replication.­­