Chromatinization ofEscherichia coliwith archaeal histones

Abstract

ABSTRACTNucleosomes restrict DNA accessibility throughout eukaryotic genomes, with repercussions for replication, transcription, and other DNA-templated processes. How this globally restrictive organization emerged from a presumably more open ancestral state remains poorly understood. Here, to better understand the challenges associated with establishing globally restrictive chromatin, we express histones in a naïve bacterial system that has not evolved to deal with nucleosomal structures:Escherichia coli. We find that histone proteins from the archaeonMethanothermus fervidusassemble on theE. colichromosomein vivoand protect DNA from micrococcal nuclease digestion, allowing us to map binding footprints genome-wide. We provide evidence that nucleosome occupancy along theE. coligenome tracks intrinsic sequence preferences but is disturbed by ongoing transcription and replication. Notably, we show that higher nucleosome occupancy at promoters and across gene bodies is associated with lower transcript levels, consistent with local repressive effects. Surprisingly, however, this sudden enforced chromatinization has only mild repercussions for growth, suggesting that histones can become established as ubiquitous chromatin proteins without interfering critically with key DNA-templated processes. Our results have implications for the evolvability of transcriptional ground states and highlight chromatinization by archaeal histones as a potential avenue for controlling genome accessibility in synthetic prokaryotic systems.