Biogeographic conservation of the cytosine epigenome in the globally important marine, nitrogen‐fixing cyanobacterium Trichodesmium

Abstract

Cytosine methylation has been shown to regulate essential cellular processes and impact biological adaptation. Despite its evolutionary importance, only a handful of bacterial, genome-wide cytosine studies have been conducted, with none for marine bacteria. Here, we examine the genome-wide, C -Methyl-cytosine (m5C) methylome and its correlation to global transcription in the marine nitrogen-fixing cyanobacterium Trichodesmium. We characterize genome-wide methylation and highlight conserved motifs across three Trichodesmium isolates and two Trichodesmium metagenomes, thereby identifying highly conserved, novel genomic signatures of potential gene regulation in Trichodesmium. Certain gene bodies with the highest methylation levels correlate with lower expression levels. Several methylated motifs were highly conserved across spatiotemporally separated Trichodesmium isolates, thereby elucidating biogeographically conserved methylation potential. These motifs were also highly conserved in Trichodesmium metagenomic samples from natural populations suggesting them to be potential in situ markers of m5C methylation. Using these data, we highlight predicted roles of cytosine methylation in global cellular metabolism providing evidence for a 'core' m5C methylome spanning different ocean regions. These results provide important insights into the m5C methylation landscape and its biogeochemical implications in an important marine N -fixer, as well as advancing evolutionary theory examining methylation influences on adaptation.

Cytosine N4-Methylation via M.Ssp6803II Is Involved in the Regulation of Transcription, Fine- Tuning of DNA Replication and DNA Repair in the Cyanobacterium Synechocystis sp. PCC 6803

“…PCC 7120 (Matveyev et al, 2001; Elhai, 2015). There are some hints that the cyanobacterial methylome could be modified in response to certain environmental cues (Walworth et al, 2017; Hu et al, 2018), but the overall role of DNA methylation beyond RM systems has not been studied in cyanobacteria so far.…”

Recent Advances in the Genomic Profiling of Bacterial Epigenetic Modifications

“…Therefore, the method can be used to identify DNA methylation in a known sequence of the genome. The 5‐methylcytosine binding complex, a ferrocene cucurbit uril (Fc⊂CB), can be used to discriminate 5‐methylcytosine and cytosine. Fc⊂CB binding to 5‐methylcytosine and cytosine produces different fluctuations of ionic currents in nanopores that can be clearly recorded and detected .…”

“…The 5‐methylcytosine binding complex, a ferrocene cucurbit uril (Fc⊂CB), can be used to discriminate 5‐methylcytosine and cytosine. Fc⊂CB binding to 5‐methylcytosine and cytosine produces different fluctuations of ionic currents in nanopores that can be clearly recorded and detected . The 75‐amino acid region of the methyl DNA binding protein MBD1 is used for labeling methylated DNA bases in epigenetics analyses via nanopores .…”

“…DNA epigenetic modifications play important roles in multiple cellular processes. For example, 6m A modifications at GATC and GANTC (N = A, T, C, or G) motifs, catalyzed by DNA adenine methylase (Dam), and cell cycle‐regulated methylase (CcrM), respectively, are involved in DNA replication, chromosome segregation, transcriptional regulation, virulence, DNA repair, and cell cycle control, etc . Distinct from the methylation of nucleobases, DNA phosphorothioate (PT) modification is a newly identified type of epigenetic modification in which the non‐bridging oxygen in the sugar‐phosphate backbone is substituted with sulfur in a sequence‐selective and R P stereo‐specific manner .…”

Cytosine Methylation Within Marine Sediment Microbial Communities: Potential Epigenetic Adaptation to the Environment

“…These modified bases comprise an organism’s methylome and are generally formed by two different MTase activities: “maintenance” and “ de novo ” methylation (Bird, 2002; Kuhlmann et al., 2005). While DNA methylation is an integral part of RM systems involved in the recognition of self vs. non-self DNA for cellular defense and mismatch repair during DNA replication, growing evidence indicates that prokaryotes can utilize both adenine and cytosine methylation as a means of regulating gene expression (Low et al., 2001; Reisenauer and Shapiro, 2002; Løbner-Olesen et al., 2005; Srikhanta et al., 2005, 2009; Wion and Casadesús, 2006; Low and Casadesús, 2008; Collier, 2009; Marinus and Casadesús, 2009; Brunet et al., 2011; Kahramanoglou et al., 2012; Gonzalez et al., 2014; Blow et al., 2016; Walworth et al., 2017; Hiraoka et al., 2019). Individual genes have been shown to be under methylation control, for example, the pap operon in Escherichia coli , and cellular cycle events have also been shown to be controlled by methylation events in the Gammaproteobacteria (Casadesús and Low, 2006).…”