Prevalence of phase variable epigenetic invertons among host-associated bacteria.

Prevalence of phase variable epigenetic invertons among host-associated bacteria.
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宿主相关细菌中相变表观遗传反转子的流行率

DOI:
10.1093/nar/gkaa907
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发表时间:
2020-11-18
影响因子:
14.9
通讯作者:
Zhang JR
Zhang JR
中科院分区:
生物学2区
文献类型:
--
作者:
Huang X;Wang J;Li J;Liu Y;Liu X;Li Z;Kurniyati K;Deng Y;Wang G;Ralph JD;De Ste Croix M;Escobar-Gonzalez S;Roberts RJ;Veening JW;Lan X;Oggioni MR;Li C;Zhang JR

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I型限制-修饰(R-M)系统由DNA内切酶(HsdR、HsdM和HsdS亚基)和甲基转移酶(HsdM和HsdS亚基)组成。在某些类型的R-M系统中,hsdS序列两侧有反向重复序列(称为表观遗传倒子),经历转化酶催化的逆转。以前对肺炎链球菌的研究表明,克隆群体中的hsdS倒置产生了在甲基组、细胞生理学和毒力方面存在深刻差异的亚群。在这项研究中,我们从16个细菌门中生物信息地鉴定了六个主要的酪氨酸和丝氨酸家族转化酶同源物,它们可能催化表观遗传的反转子中的hsdS反转。特别是,表观遗传倒子高度富含与宿主相关的细菌。我们进一步验证了四个具有代表性的宿主相关细菌的I型R-M系统中的hsdS倒置,发现每个产生的hsdS等位基因变体都指定了一个唯一的DNA序列的甲基化。此外,转录组分析表明,粪肠球菌的hsdS等位基因变异对基因表达有显著影响。这些发现表明,由表观遗传倒子中的转化子驱动的表观遗传开关广泛地作用于宿主相关细菌,这可能在I型R-M系统对抗噬菌体感染之外的细菌宿主适应和毒力方面做出广泛贡献。
Abstract Type I restriction-modification (R-M) systems consist of a DNA endonuclease (HsdR, HsdM and HsdS subunits) and methyltransferase (HsdM and HsdS subunits). The hsdS sequences flanked by inverted repeats (referred to as epigenetic invertons) in certain Type I R-M systems undergo invertase-catalyzed inversions. Previous studies in Streptococcus pneumoniae have shown that hsdS inversions within clonal populations produce subpopulations with profound differences in the methylome, cellular physiology and virulence. In this study, we bioinformatically identified six major clades of the tyrosine and serine family invertases homologs from 16 bacterial phyla, which potentially catalyze hsdS inversions in the epigenetic invertons. In particular, the epigenetic invertons are highly enriched in host-associated bacteria. We further verified hsdS inversions in the Type I R-M systems of four representative host-associated bacteria and found that each of the resultant hsdS allelic variants specifies methylation of a unique DNA sequence. In addition, transcriptome analysis revealed that hsdS allelic variations in Enterococcus faecalis exert significant impact on gene expression. These findings indicate that epigenetic switches driven by invertases in the epigenetic invertons broadly operate in the host-associated bacteria, which may broadly contribute to bacterial host adaptation and virulence beyond the role of the Type I R-M systems against phage infection.
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