Polyphosphate drives bacterial heterochromatin formation.

Autor: Beaufay F; Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA., Amemiya HM; Cellular and Molecular Biology Program, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA.; Department of Computational medicine and Bioinformatics, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA., Guan J; Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA., Basalla J; Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA., Meinen BA; Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.; Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI, USA., Chen Z; Biophysics Program, University of Michigan, Ann Arbor, MI, USA., Mitra R; Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA., Bardwell JCA; Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.; Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI, USA., Biteen JS; Biophysics Program, University of Michigan, Ann Arbor, MI, USA.; Department of Chemistry, University of Michigan, Ann Arbor, MI, USA., Vecchiarelli AG; Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA., Freddolino PL; Department of Biological Chemistry, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA., Jakob U; Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.; Department of Biological Chemistry, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2021 Dec 24; Vol. 7 (52), pp. eabk0233. Date of Electronic Publication: 2021 Dec 22.
DOI: 10.1126/sciadv.abk0233
Abstrakt: Heterochromatin is most often associated with eukaryotic organisms. Yet, bacteria also contain areas with densely protein-occupied chromatin that appear to silence gene expression. One nucleoid-associated silencing factor is the conserved protein Hfq. Although seemingly nonspecific in its DNA binding properties, Hfq is strongly enriched at AT-rich DNA regions, characteristic of prophages and mobile genetic elements. Here, we demonstrate that polyphosphate (polyP), an ancient and highly conserved polyanion, is essential for the site-specific DNA binding properties of Hfq in bacteria. Absence of polyP markedly alters the DNA binding profile of Hfq, causes unsolicited prophage and transposon mobilization, and increases mutagenesis rates and DNA damage–induced cell death. In vitro reconstitution of the system revealed that Hfq and polyP interact with AT-rich DNA sequences and form phase-separated condensates, a process that is mediated by the intrinsically disordered C-terminal extensions of Hfq. We propose that polyP serves as a newly identified driver of heterochromatin formation in bacteria.
Databáze: MEDLINE