Project description
A closer look at chromatin evolution and complexity
Chromatin is a complex of DNA, RNA and proteins that makes up chromosomes. It plays an important role in regulating gene expression, and DNA replication and repair. In eukaryotes, chromatin is organised into repeating units called nucleosomes, which consist of DNA wrapped around histone proteins. Eukaryotic chromatin evolved from a simpler form of chromatin that was present in a prokaryotic ancestor. Funded by the European Research Council, the 3DchromArchaea project will shed light on the origins of chromatin complexity in eukaryotes. It will study the 3D organisation of chromatin in archaea, which are prokaryotic but also use histones to organise their genomes. 3DchromArchaea will employ state-of-the-art cryo-electron microscopy to study the structure of chromatin in selected archaeal systems in situ and in vitro.
Objective
This proposal brings together the field of chromatin evolution and state-of-the-art structural biology to advance our understanding of a fundamental question: origin of chromatin structural and regulatory complexity.
Eukaryotes and most groups of archaea organize their genomes in the form of histone-based chromatin. Conservation of histones across the tree of life goes beyond protein sequence and histone fold. Tertiary arrangement of histones and DNA geometry in archaeal nucleosomes resemble those in eukaryotes; however, archaea can form special hypernucleosomes and “slinky”-like arrangements. Similarly to eukaryotes, some archaea have multiple histone variants and extended histone tails, although it is unclear whether their structural and regulatory roles are conserved. Eukaryotes inherited histone-based chromatin from archaea, however, the origins of eukaryotic chromatin complexity are enigmatic.
Therefore, this proposal will address the 3D organization of chromatin in archaea to advance the understanding of chromatin evolution. We will test the following hypotheses: archaeal chromatin along with hypernucleosomes contains multiple open structures to maintain DNA accessibility and allow polymerase passage; histone variant exchange and histone tails in archaea play an important role in chromatin compaction similarly to eukaryotes. To test our hypotheses, we will synergistically apply state-of-the-art cryo-electron microscopy (cryo-EM) in situ and in vitro to selected archaeal systems. In situ cryo-EM will provide structural information about chromatin in native context, while cryo-EM of in vitro reconstituted chromatin will provide high-resolution structural information. Structural analysis complemented with biochemical, biophysical characterization and nucleosome positioning data will provide insights into 3D chromatin architecture in archaea in the context of eukaryotic chromatin evolution.
Fields of science
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Topic(s)
Funding Scheme
ERC - Support for frontier research (ERC)Host institution
69117 Heidelberg
Germany