Distinct heterochromatin‐like domains promote transcriptional memory and silence parasitic genetic elements in bacteria

Abstract

There is increasing evidence that prokaryotes maintain chromosome structure, which in turn impacts gene expression. We recently characterized densely occupied, multi‐kilobase regions in the E. coli genome that are transcriptionally silent, similar to eukaryotic heterochromatin. These extended protein occupancy domains (EPODs) span genomic regions containing genes encoding metabolic pathways as well as parasitic elements such as prophages. Here, we investigate the contributions of nucleoid‐associated proteins (NAPs) to the structuring of these domains, by examining the impacts of deleting NAPs on EPODs genome‐wide in E. coli and B. subtilis. We identify key NAPs contributing to the silencing of specific EPODs, whose deletion opens a chromosomal region for RNA polymerase binding at genes contained within that region. We show that changes in E. coli EPODs facilitate an extra layer of transcriptional regulation, which prepares cells for exposure to exotic carbon sources. Furthermore, we distinguish novel xenogeneic silencing roles for the NAPs Fis and Hfq, with the presence of at least one being essential for cell viability in the presence of domesticated prophages. Our findings reveal previously unrecognized mechanisms through which genomic architecture primes bacteria for changing metabolic environments and silences harmful genomic elements.SynopsisE. coli extended protein occupancy domains (EPODs) are densely occupied and transcriptionally silent genomic regions resembling eukaryotic heterochromatin. Here, studies of nucleoid‐associated proteins (NAPs) and their contributions to EPOD structuring suggests that they serve to allow efficient metabolic transitions and minimize leaky expression of prophages.Several E. coli NAPs contribute to structuring of EPODs.Different combinations of NAPs give rise to distinct EPOD subtypes.EPODs play an essential role in silencing potentially harmful genomic elements.EPODs appear to regulate many metabolic genes and allow efficient responses upon repeated induction.Distinct heterochromatin‐like domains promote transcriptional memory and silence parasitic genetic elements in bacteria.