title: In vivo targeting of de novo DNA methylation by histone modifications in yeast and mouse.
abstract: Methylation of cytosines (5(me)C) is a widespread heritable DNA modification. During mammalian development, two global demethylation events are followed by waves of de novo DNA methylation. In vivo mechanisms of DNA methylation establishment are largely uncharacterized. Here, we use Saccharomyces cerevisiae as a system lacking DNA methylation to define the chromatin features influencing the activity of the murine DNMT3B. Our data demonstrate that DNMT3B and H3K4 methylation are mutually exclusive and that DNMT3B is co-localized with H3K36 methylated regions. In support of this observation, DNA methylation analysis in yeast strains without Set1 and Set2 shows an increase of relative 5(me)C levels at the transcription start site and a decrease in the gene-body, respectively. We extend our observation to the murine male germline, where H3K4me3 is strongly anti-correlated while H3K36me3 correlates with accelerated DNA methylation. These results show the importance of H3K36 methylation for gene-body DNA methylation in vivo.
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.
authors.forename: Marco
authors.initials: M
authors.lastname: Morselli
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.
authors.forename: William A
authors.initials: WA
authors.lastname: Pastor
authors.affiliation: Biochemistry and Molecular Biology Unit, Department of Life Sciences, Laboratory of Functional Genomics and Protein Engineering, Parma, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Montanini
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.
authors.forename: Kevin
authors.initials: K
authors.lastname: Nee
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ferrari
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.
authors.forename: Kai
authors.initials: K
authors.lastname: Fu
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.|Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, United States.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Bonora
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.
authors.forename: Liudmilla
authors.initials: L
authors.lastname: Rubbi
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.
authors.forename: Amander T
authors.initials: AT
authors.lastname: Clark
authors.affiliation: Biochemistry and Molecular Biology Unit, Department of Life Sciences, Laboratory of Functional Genomics and Protein Engineering, Parma, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Ottonello
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.|Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, United States.|Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United States.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Jacobsen
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.|Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, United States.
authors.forename: Matteo
authors.initials: M
authors.lastname: Pellegrini
mesh_terms: D000818:Animals; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D018899:CpG Islands; D003596:Cytosine / Q000378:metabolism; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental; D005822:Genetic Vectors; D005854:Germ Cells; D011495:Histone-Lysine N-Methyltransferase / Q000172:deficiency / Q000235:genetics; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008780:Methyltransferases / Q000172:deficiency / Q000235:genetics; D051379:Mice; D016366:Open Reading Frames; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D015398:Signal Transduction; D024363:Transcription Initiation Site; D014170:Transformation, Genetic; D000097584:DNA Methyltransferase 3B
chemical_list: D002843:Chromatin; D003596:Cytosine; D004248:DNA (Cytosine-5-)-Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones; D008780:Methyltransferases; D020033:Protein Isoforms; D029701:Saccharomyces cerevisiae Proteins; D000097584:DNA Methyltransferase 3B; C448996:Set2 protein, S cerevisiae; C411250:SET1 protein, S cerevisiae
keywords: DNA methylation; DNMT3; H3K36me3; H3K4me3; S. cerevisiae; developmental biology; evolutionary biology; genomics; histone; mouse; stem cells
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