title: The Epigenomic Landscape of Prokaryotes.
abstract: DNA methylation acts in concert with restriction enzymes to protect the integrity of prokaryotic genomes. Studies in a limited number of organisms suggest that methylation also contributes to prokaryotic genome regulation, but the prevalence and properties of such non-restriction-associated methylation systems remain poorly understood. Here, we used single molecule, real-time sequencing to map DNA modifications including m6A, m4C, and m5C across the genomes of 230 diverse bacterial and archaeal species. We observed DNA methylation in nearly all (93%) organisms examined, and identified a total of 834 distinct reproducibly methylated motifs. This data enabled annotation of the DNA binding specificities of 620 DNA Methyltransferases (MTases), doubling known specificities for previously hard to study Type I, IIG and III MTases, and revealing their extraordinary diversity. Strikingly, 48% of organisms harbor active Type II MTases with no apparent cognate restriction enzyme. These active 'orphan' MTases are present in diverse bacterial and archaeal phyla and show motif specificities and methylation patterns consistent with functions in gene regulation and DNA replication. Our results reveal the pervasive presence of DNA methylation throughout the prokaryotic kingdoms, as well as the diversity of sequence specificities and potential functions of DNA methylation systems.
authors: Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America.|U.S. Department of Energy Joint Genome Institute, Walnut Creek, California, United States of America.
authors: Matthew J
authors: MJ
authors: Blow
authors: Pacific Biosciences, Menlo Park, California, United States of America.
authors: Tyson A
authors: TA
authors: Clark
authors: Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America.|U.S. Department of Energy Joint Genome Institute, Walnut Creek, California, United States of America.
authors: Chris G
authors: CG
authors: Daum
authors: Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America.
authors: Adam M
authors: AM
authors: Deutschbauer
authors: New England Biolabs, Ipswich, Massachusetts, United States of America.
authors: Alexey
authors: A
authors: Fomenkov
authors: Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America.|U.S. Department of Energy Joint Genome Institute, Walnut Creek, California, United States of America.
authors: Roxanne
authors: R
authors: Fries
authors: Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America.|U.S. Department of Energy Joint Genome Institute, Walnut Creek, California, United States of America.
authors: Jeff
authors: J
authors: Froula
authors: Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America.|U.S. Department of Energy Joint Genome Institute, Walnut Creek, California, United States of America.
authors: Dongwan D
authors: DD
authors: Kang
authors: Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America.|U.S. Department of Energy Joint Genome Institute, Walnut Creek, California, United States of America.
authors: Rex R
authors: RR
authors: Malmstrom
authors: New England Biolabs, Ipswich, Massachusetts, United States of America.
authors: Richard D
authors: RD
authors: Morgan
authors: New England Biolabs, Ipswich, Massachusetts, United States of America.
authors: Janos
authors: J
authors: Posfai
authors: Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America.|U.S. Department of Energy Joint Genome Institute, Walnut Creek, California, United States of America.
authors: Kanwar
authors: K
authors: Singh
authors: Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America.|U.S. Department of Energy Joint Genome Institute, Walnut Creek, California, United States of America.
authors: Axel
authors: A
authors: Visel
authors: Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America.
authors: Kelly
authors: K
authors: Wetmore
authors: Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America.|U.S. Department of Energy Joint Genome Institute, Walnut Creek, California, United States of America.
authors: Zhiying
authors: Z
authors: Zhao
authors: Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America.|U.S. Department of Energy Joint Genome Institute, Walnut Creek, California, United States of America.
authors: Edward M
authors: EM
authors: Rubin
authors: Pacific Biosciences, Menlo Park, California, United States of America.
authors: Jonas
authors: J
authors: Korlach
authors: Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America.|U.S. Department of Energy Joint Genome Institute, Walnut Creek, California, United States of America.
authors: Len A
authors: LA
authors: Pennacchio
authors: New England Biolabs, Ipswich, Massachusetts, United States of America.
authors: Richard J
authors: RJ
authors: Roberts
mesh_terms: D017124:Conserved Sequence; D019175:DNA Methylation / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D015280:DNA Restriction-Modification Enzymes / Q000145:classification / Q000378:metabolism; D057890:Epigenomics; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D016678:Genome; D008780:Methyltransferases / Q000378:metabolism; D058977:Molecular Sequence Annotation; D005810:Multigene Family; D059372:Nucleotide Motifs / Q000235:genetics; D010802:Phylogeny; D011387:Prokaryotic Cells / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D015280:DNA Restriction-Modification Enzymes; D008780:Methyltransferases