Transcription and histone-based chromatin in archaea
Speaker: Prof. Finn Werner, RNAP laboratory, Institute for Structural and Molecular Biology, University College London
Host: Qunxin She, Section for Functional Genomics
The archaeal transcription apparatus is closely related to the eukaryotic RNAPII-system in terms of RNA polymerase subunit composition and structure, utilisation of general transcription factors, promoter consensus motifs - and regulatory networks (1). This similarity extends to the chromatinised DNA template of transcription. Many euryarchaea encode distinct types of histones, but the role of histone-based chromatin for transcription regulation has remained opaque (2).
We have characterised the structure and function of the canonical histone A3 and the histone variant 1647 in the hyperthermophile M. jannaschii using a multidisciplinary strategy. While canonical histones wrap DNA akin to their eukaryotic derivatives, the variant histone is capable of bridging DNA, forming loops and thereby bringing distant regions of the genome in proximity. This crosslinking activity is dependent on the tetramerisation property of 1647 and enabled by the variant-specific C-terminal domain – and is potentially the target for regulation. Comparisons between nucleosome sequencing profiling (reflecting histone occupancy in vivo) and competition between transcription complexes and histones in vitro, reveal that the two types of histones have different effects on transcription. While both histones are capable of inhibiting transcription elongation, only the 1647 variant is refractive to the formation of transcription preinitiation complexes on promoters. Varying expression levels of 1647 in vivo would thus not only affect overall compaction of the genome by looping, but also repress transcription at the level of initiation.
An intriguing picture is emerging where the architecture of the archaeal genome is influenced by wrapping and bridging histones with important implications not only for gene expression, but also for antiviral defence, DNA replication, -repair and –recombination.