Polyphosphate drives bacterial heterochromatin formation
Polyphosphate drives bacterial heterochromatin formation
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DOI：
10.1126/sciadv.abk0233
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发表时间：
2021-12-01
期刊：
影响因子：
13.6
通讯作者：
Jakob, Ursula
中科院分区：
文献类型：
--
作者：
Beaufay, Francois;Amemiya, Haley M.;Jakob, Ursula
异染色质通常与真核生物有关。然而，细菌也含有密集的蛋白质占据的染色质，似乎沉默基因表达的区域。一种与核相关的沉默因子是保守蛋白Hfq。虽然看起来在其DNA结合特性上是非特异性的，但Hfq在富含AT的DNA区域强烈富集，这是前噬菌体和移动的遗传元件的特征。在这里，我们证明了聚磷酸盐（polyP），一个古老的和高度保守的聚阴离子，是必不可少的定点DNA结合特性的Hfq在细菌中。polyP的缺失显著改变了Hfq的DNA结合谱，引起主动的原噬菌体和转座子动员，并增加诱变率和DNA损伤诱导的细胞死亡。在体外重建的系统显示，Hfq和polyP与AT丰富的DNA序列相互作用，并形成相分离的缩合物，这是一个过程，介导的内在无序的Hfq的C-末端延伸。我们认为polyP是细菌中异染色质形成的一个新发现的驱动因素。
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 poly-phosphate (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.