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RESEARCH PRODUCT

Deciphering the Rules Underlying Xenogeneic Silencing and Counter-Silencing of Lsr2-like Proteins Using CgpS of Corynebacterium glutamicum as a Model

Johanna WiechertAndrei FilipchykMax HünnefeldCornelia GätgensJannis BrehmRalf HeermannJulia Frunzke

subject

Molecular Biology and PhysiologyGene Transfer HorizontalactinobacteriaMicrobiologyQR1-502Corynebacterium glutamicumDNA-Binding Proteinsregulatory networksBacterial Proteinslsr2ddc:570xenogeneic silencinghorizontal gene transferGene Silencingcounter-silencingat-rich dnaProtein BindingTranscription FactorsResearch Article

description

In actinobacteria, Lsr2-like nucleoid-associated proteins function as xenogeneic silencers (XS) of horizontally acquired genomic regions, including viral elements, virulence gene clusters in Mycobacterium tuberculosis, and genes involved in cryptic specialized metabolism in Streptomyces species. Consequently, a detailed mechanistic understanding of Lsr2 binding in vivo is relevant as a potential drug target and for the identification of novel bioactive compounds. Here, we followed an in vivo approach to investigate the rules underlying xenogeneic silencing and counter-silencing of the Lsr2-like XS CgpS from Corynebacterium glutamicum. Our results demonstrated that CgpS distinguishes between self and foreign by recognizing a distinct drop in GC profile in combination with a short, sequence-specific motif at the nucleation site. Following a synthetic counter-silencer approach, we studied the potential and constraints of transcription factors to counteract CgpS silencing, thereby facilitating the integration of new genetic traits into host regulatory networks.

10.1128/mbio.02273-19https://doaj.org/article/d7f7c3ae09644c0ea3c1f96caa6c2f9f